SK405288A3 - N-phenylpyrazole derivatives, method for producing the same, intermediate products, insecticidal agents and their use to kill insect - Google Patents

Abstract

N-Phenylpyrazole derivatives of the formula: <CHEM> wherein R<1> represents cyano, nitro, halogen, acetyl or formyl: R<2> represents R<5>SO2, R<5>SO or R<5>S in which R<5> is optionally halogen substituted alkyl, alkenyl or alkynyl; R<3> represents a hydrogen atom or a group NR<6>R<7> wherein R<6> and R<7> each represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R<6> and R<7> together form a cyclic imide and R<4> represents a substituted phenyl group possess arthropodicidal, plant nematocidal, anthelmintic and anti-protozoal properties; their preparation, compositions containing them and their use are described.

Description

N-phenylpyrazole derivatives, process for their preparation, intermediates, insecticides and their use for insect control

Technical field

The present invention relates to N-phenylpyrazole derivatives, processes for their preparation, insecticidal compositions containing them as active ingredients, and the use of these compounds and insect control agents.

BACKGROUND OF THE INVENTION

Several pyrazoles (heterocycles containing 2 nitrogen atoms) are well known as insecticides. Certain compounds containing a pyrrole group (heterocycle containing 1 nitrogen atom) are also known as insecticides. However, these substances usually contain in their. other chemical groups known to exhibit insecticidal activity, such as a pyrethroid group, a carbamate moiety, or a particular organophosphorus group, are also known to be present in the molecule. Single substituted pyrrole derivatives for use in agriculture have been described, for example, in British Pat. 2,189,242, but only for fungicidal application.

SUMMARY OF THE INVENTION; and

Accordingly, the invention provides N-phenylpyrazole derivatives of Formula I

in which

R 6 represents cyano, nitro, halogen, i. fluorine, chlorine, bromine or iodine, acetyl or formyl,

R ² is a radical R ⁵ with _Z, R ^a SO or R ^a S in which R ^a represents straight or branched alkyl, alkenyl or alkynyl group (preferably l- (alkynyl) alkyl and more preferably 2-alkynyl) containing the 4 carbon atoms, optionally substituted by one or more identical or different halogen atoms,

R ³ represents a hydrogen atom or an amino group of the formula

NR ^e R ⁷ where

R ⁶ and R ⁷ , which may be the same or different, each represent a hydrogen atom, a straight or branched alkyl, alkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms each, a formyl group or a straight or branched alkanoyl group containing 2 to 5 carbon atoms and optionally substituted by one or more halogen atoms, or ^R and R ⁷ together with the nitrogen to which they are bound, form a five or six-membered cyclic imido, or are straight or branched alkoxycarbonyl having 2 to 5 carbon atoms and optionally substituted by one or more halogen or R ³ represents a straight or branched (C 2 -C 5) alkoxymethyleneamino group optionally substituted on the methylene moiety with a straight or branched (C 1 -C 4) alkyl group, or a halogen atom, i. fluorine, chlorine, bromine or iodine; and

R ⁴ represents a phenyl group substituted in the 2-position by a fluorine, chlorine, bromine or iodine atom, in the 4-position a straight or branched C 1 -C 4 alkyl or alkoxy group optionally substituted by one or more identical or different halogen atoms (preferably trifluoromethyl) or trifluoromethoxy), or a chlorine or bromine atom, and in the 6-position optionally substituted by a fluorine, chlorine, bromine or iodine atom, with the exception of a compound wherein R ¹ is cyano, R ² is methanesulfonyl, R ³ is amino and R ⁴ is 2 6-Dichloro-4-trifluoromethylphenyl which have valuable activity against harmful arthropods, nematodes of harmful plants, helminths and protozoa, especially when arthropods ingest a compound or compounds of formula I.

The present invention relates to compositions comprising the aforementioned active substances and a process for the preparation of such active substances.

It should be noted that the halogen atoms on the phenyl group in the meaning of R ⁴ may be the same or different. If the respective groups are substituted by more than one halogen atom, the halogen atoms may be the same or different.

Preferred are those compounds of formula I wherein R ² is C 1 -C 4 alkylsulfonyl, -sulfinyl or -thio, optionally halo-substituted, or alkenyl- or alkynylsulfonyl, -sulfinyl, or -halo of up to 4 carbon atoms and optionally halogenated, preferably trifluoromethylthio or trifluoromethylsulfinyl, R ³ is hydrogen, amino or methylamino, and R ¹ is halogen or preferably cyano or nitro.

Compounds of formula I wherein R ⁴ contains trifluoromethyl or trifluoromethoxy and R ² is an optionally halogenated alkylsulfonyl, -sulfinyl or -thio group having 1 to 4 carbon atoms are preferred. Particularly preferred features of R ² include trifluoromethylthio, trifluoromethylsulphinyl and trifluoromethylsulfonyl.

Preferred are compounds of formula I wherein R ⁴ is 2,4,6-trichlorophenyl, 2,6-dichloro-4-difluoromethoxyphenyl, 2-chloro-4-trifluoromethyl, 2-bromo-6-chloro-4-trifluoromethylphenyl, 2,6-dibromo-4-trifluoromethylphenyl;

2-bromo-4-trifluoromethylphenyl.

Particularly preferred are compounds of formula I wherein R ⁴ is 2,6-dichloro-4-trifluoromethylphenyl or 2,6-dichloro-4-trifluoromethoxyphenyl.

Of particular interest are the following compounds of formula I:

1. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

2. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylthiopyrazole

3. 5-Amino-3-cyano-1- (2,6-dichloro-4-difluoromethoxyphenyl) -4-trifluoromethylthiopyrazole

4. 5-Amino-1- (2-chloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole

5. 5-Amino-3-cyano-1- (2,4,6-trichlorophenyl) -4-trifluoromethylthiopyrazole

6. 5-Amino-3-cyano-1- (2,6-dibromo-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

7. 5-Amino-1- (2-bromo-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole

8. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-difluoromethylthiopyrazole

9. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-heptafluoropropylthiopyrazole

10. 5-Amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole

11. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trichloromethylthiopyrazole

12. 5-Amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

13. 5-Amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

14. 5-Amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoro-4-trifluoromethylthiopyrazole

15. 5-Amino-4-chlorodifluoromethylthio-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole

I

16. 5-Chloro-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

17. 5-Amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

18. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-trifluoromethylthiopyrazole

19. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxyethylidenamino-4-trifluoromethylthiopyrazole

20. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-methanesulfonylpyrazole

21. 5-Acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

22. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (propionyl) amino-4-trifluoromethylthiopyrazole

23. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propionamido-4-trifluoromethylthiopyrazole

24. 5-Acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

25. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthio-5-trimethylacetamidopyrazole

26. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (methoxycarbonyl) amino-4-trifluoromethylthiopyrazole

27. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-trifluoromethylthiopyrazole

28. 5-Chloroacetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

29. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-methanesulfonylpyrazole

30. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonyl-5-trimethylacetamidopyrazole

31. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino-4-trifluoromethylthiopyrazole

32. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-isopropylamino-4-trifluoromethylthiopyrazole

Ί

3. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propylamino-4-trifluoromethylthiopyrazole

34. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dipropylamino-4-trifluoromethylthiopyrazole

35. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (propargyl) amino-4-trifluoromethylthiopyrazole

36. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-methylamino-4-methanesulfonylpyrazole

37. 5-Bromo-3-cyano-1- (2,6-dichloro-4-trifluoroethylphenyl) -4-trifluoromethanesulfonylpyrazole

38. 5-Bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

39. 5-Bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

40. 5-Amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

41. 3-Bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

42. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

43. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole

44. 3-Cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylthiopyrazole

45. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

46. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-iodo-4-trifluoromethylthiopyrazole

47. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-iodo-4-trifluoromethanesulfonylpyrazole

48. 5-Amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-iodo-4-methanesulfonylpyrazole

49. 1- (2,6-Dichloro-4-trifluoromethyl-phenyl) -3-iodo-4-methanesulfonyl-pyrazole

50. I ^- (2,6-dichloro-4-trifluoromethylphenyl) -3-iodo-4-trifluoromethylthiopyrazole

51. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-trifluoromethanesulfonyl-pyrazole

52. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-trifluoromethylsulfinyl-pyrazole

53. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethanesulfonylpyrazole

54. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylsulfinylpyrazole

55. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole

56. 4-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4- (1-methyl-prop-2-ynylsulfinyl) -pyrazole

57. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-methylsulfinyl-pyrazole

58. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-isopropylsulfinyl-pyrazole

59. 5-Amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole

60. 5-Amino-4-tert-butanesulfonyl-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole

61. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propylamino-4-trifluoromethylsulfonylpyrazole

62. 5-Acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole

63. 1- (2,6-Dichloro-4-trifluoromethyl-phenyl) -4-methanesulfonyl-3-nitropyrazole

64. 5-Amino-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-methanesulfonyl-3-nitropyrazole

65. 1- (2,6-Dichloro-4-trifluoromethylphenyl) -3-nitro-4-trifluoromethylsulfinylpyrazole

66. 5-Amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-cyano-4-methanesulfonylpyrazole

67. 5-Amino-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -3-cyano-4-methanesulfonylpyrazole

68. 3-Acetyl-5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole

69. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole

70. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethylthiopyrazole

71. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-propylthiopyrazole

72. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-isopropylthiopyrazole

73. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (2-methylpropylthio) pyrazole

74. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (1-methylpropylthio) pyrazole

75. 4-Allylthio-5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole

76. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (prop-2-ynylthio) pyrazole

77. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (1-methylprop-2-ynylthio) pyrazole

78. 5-Amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole

79. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-tert-butylthiopyrazole

80. 5-Amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylsulfinylpyrazole

81. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-ethanesulfonyl-pyrazole

82. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-methylamino-4-trifluoromethylthiopyrazole

83. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (N-ethoxycarbonyl-N-methyl) amino-4-trifluoromethylthiopyrazole

84. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-trifluoromethyl-4-trifluoromethyl-11-pyrrolidinyl

85. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (ethoxycarbonylamino) -4-trifluoromethylthiopyrazole

86. 3-Acetyl-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

87. 1- (2,6-Dichloro-4-trifluoromethyl-phenyl) -3-formyl-4-trifluoromethyl-thiopyrazole

88. 5-Amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-formyl-4-trifluoromethylthiopyrazole

89. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-fluoro-4-trifluoromethanesulfonylpyrazole. 5-Amino-3-cyano-4-dichlorofluoromethylthio-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole

91. 5-Amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole

92. 5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-pentafluoroethylthiopyrazole

93. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino-4-trifluoromethylsulphinylpyrazole

94. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-iodo-4-trifluoromethylsulfinylpyrazole

95. 5-Bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole

96. 5-Acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole

97. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-trifluoromethanesulfonylpyrazole

98. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxycarbonylamino-4-trifluoromethanesulfonylpyrazole

99. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-trifluoromethanesulfonylpyrazole

100. 5-Amino-4- (2-chloro-1,1,2-trifluoroethylthio) -3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole

101. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino-4-trifluoromethanesulfonylpyrazole.

Numbers 1 to 101 are used to identify the above compounds in the following.

As mentioned above, the invention also relates to insecticidal compositions containing, as active ingredients, compounds of the above formula I. However, as mentioned below, the compounds of the formula I have a much broader spectrum of action and can be used as active substances for the production of other as insecticidal agents. All of these compositions will be described in the following as compositions of the invention, but it should be emphasized that the subject matter of the invention is only insecticidal compositions.

The invention also provides a method of controlling harmful arthropods, nematodes, helminths or protozoa at a particular site, which comprises treating the site with an effective amount of a compound of formula (I) in which the individual symbols are as defined above. In particular, the compounds of the formula I can be used in veterinary medicine, in livestock breeding and in health against arthropods, helminths or protozoa parasitizing, either internally or externally, on vertebrate animals, in particular on warm-blooded vertebrates such as humans and domestic animals such as bovine animals. cattle, sheep, goats, horses, pigs, poultry, dogs, cats and fish, such as Acarina mites, including ticks such as Ixodes spp.,

Boophilus spp., E.g., Boophilus microplus, Amblyomma spp.,

Hyalomma spp.

Rhipicephalus spp., Such as Rhipicephalus appendiculatus,

Haemaphysalis spp.

Dermacentor spp. and

Ornithodorus spp., Such as Ornithodorus moubata, and other species, such as Damalinia spp.,

Dermahyssus gallinae,

Sarcoptes spp., Such as Sarcoptes scabiei,

Psoroptes spp. .

Chorioptes spp. .

Demodex spp. and Eutrombicula spp., the Diptera family, such as e.g.

Aedes spp.

Anopheles spp.

Musca spp.

Hypoderma spp.

Gastrophilus spp. and Simulium spp. Hemiptera, such as Triatoma spp.

Phthiraptera, such as Damalinia spp. and Linognathus spp. , Siphonaptera, such as Ctenocephalides spp. Dictyoptera, such as Periplaneta spp. and Blatella and the order of the Hymenoptera, for example

Monomorium pharaonis, for example against infections of the gastrointestinal tract caused by parasitic nematodes such as those of the Trichostrongylidae family,

Nippostrongylus brasiliensis,

Trichinella spiralis,

Haemonchus contortus,

Trichostrongylus colubriformis,

Nematodirus battus,

Ostertagia circumcincta,

Trichostrongylus axei,

Cooperia spp. and

Hymenolepis nana, in the control and treatment of protozoal diseases caused by e.g.

Eimeria spp. . such as Eimeria tenella Eimeria acervulina Eimeria Brunetti, Eimeria maxima a Eimeria necatrix,

Trypanosoma cruzi Leishmania spp. Plasmodium spp. Babesia spp.

Trichomonadidae spp.

Histomonas spp.

Giardia spp.

Toxoplasma spp.,

Entamoeba histolytica and Theileria spp. , in the protection of stored products such as cereal products including grain and flour, groundnuts, animal feed, lumber and household goods such as carpets and textiles against arthropod infestations, in particular beetles, including various moths and mites such as

Ephestia spp. (Moth),

Anthrenus spp. (Antrénus).

Tribolium spp. (Flour beetles),

Sitophilus spp. (grain) a

Acarus spp. for the destruction of cockroaches, ants, termites and similar arthropods in residential and industrial buildings and for the control of mosquito larvae in waterways, wells, reservoirs and other standing or flowing water, for the treatment of foundations, structures and soil to protect buildings against attack termites such as

Reticulitermes spp. .

Heterotermes spp. and

Coptotermes spp., In agriculture to combat adults, larvae and eggs of Lepidoptera pests (butterflies and moths) such as

Heliothis spp. like Heliothis virescens,

Heliothis armigera and Heliothis zea,

Spodoptera spp., Such as Spodoptera exempta, Spodoptera littoralis and Spodoptera eridania,

Mamestra configurata (sea),

Earias spp. like Earias insulana,

Pectinophora spp., Such as Pectinophora gossypiella,

Ostrinia spp., Such as Ostrinia nubilalis (corn windbreaker), Trichoplusia ni,

Pieris spp. (Miller),

Laphygma spp.,

Agrotis spp., And Amathes spp. (Cutworms),

Wiseana spp.

Chilo spp.

Tryporyza spp. and Diatraea spp.,

Sparganothis pilleriana,

Cydia pomonella,

Archips spp.

Plutella xylostella (mole) against adult beetles and beetle larvae (Coleoptera), such as

Hypothenemus hampei,

Hylesinus spp. (Lykokaz).

Anthonomus grandis,

Acalymma spp.

Lema spp. (Cuckoo).

Psylliodes spp. (Drobčík).

Leptinotarsa decemlineata,

Diabrotica spp.

Gonocephalum spp. (Flour beetles),

Agriotes spp. (Kováčik).

Dermolepida and Heteronychus spp.,

Phaedon cochleariae,

Lissorhoptrus oryzophilus,

Meligethes spp. (Pollen beetles),

Ceutorhynchus spp. (Skrytonos).

Rhynchophorus and Cospomolites spp., Against Hemipter pests such as e.g.

Psylla spp. (Measured).

Bemisia spp.

Trialeurodes spp. (White flies),

Aphis spp. .

Myzus spp. .

Megoura viciae,

Phylloxera spp. .

Adelges spp. .

Phorodom humuli,

Aeneolamia spp

Nephotettix spp.

Empoasca spp. (Cikádočka).

Nilaparvata spp.,

Perkinsiella spp.

Pyrilla spp.

Aonidiella spp.

Coccus spp.

Pseudococcús spp. (Scarlet).

Helopeltis spp.

Lygus spp. .

Dysdercus spp.

Oxycarenus spp. and

Nezara spp., Against Hymenoptera pests such as

Athalia spp. (Sawflies),

Cephus spp. (thistle) a

Atta spp., Against Diptera pests such as

Hylemyia spp. (Boll).

Atherigona spp.

Chlorops spp. (Springtails}

Phytomyza spp. (Minus) a

Ceratitis spp. (propellers), against Thysanoptera pests, such as

Thrips tabaci, against Orthoptera pests such as Locusta and Schistocerca spp. And vipers (e.g. Gryllus spp. And Acheta spp.), Collembola pests such as they are for example

Sminthurus spp. and

Oriychiurus spp. Against pests of the Isoptera family, such as

Odontotermes spp., (Termites), against the Dermaptera, such as

Forficula spp. (ucholak) as well as against other arthropods important in the agricultural field, such as mites, for example

Tetranychus spp. (Mite),

Panonychus spp.

Bryobia spp. (Mite),

Eriophyes spp. (bellows) a

Polyphagotarsonemus spp., Infra

Blaniulus spp. (Bodkavka).

Scutigerella spp. (Drobnonôžka).

Oniscus spp. (chewing gum) a

Triops spp. (plant), against nematodes attacking plants and trees relevant to agriculture, forestry and horticulture, either directly or by spreading bacterial, viral, mycoplasmic or fungal plant diseases, and against root and other nematodes such as

Meloidogyne spp. , such as M. incognita,

Globodera spp., Such as G. rostochiensis,

Heterodera spp., E.g. H. avenae,

Radopholus spp., For example R. similis,

Pratylenchus spp., For example P. pratensis,

Belonolaimus spp., For example B. gracilis,

Tylenchulus spp., For example T. semipenetrans,

Rotylenchulus spp., For example R. reniformis,

Rotylenchus spp., For example R. robustus,

Helicotylenchus spp., For example H. multicinctus,

Hemicycliophora spp., For example H. gracilis,

Criconemoides spp., For example C. similis,

Trichodorus spp., For example T. primitivus,

Xiphinema spp., For example X. diversicaudatum,

Longidorus spp., Such as L. elongatus,

Hoplolaimus spp., For example H. coronatus,

Aphelenchoides spp., For example, A. ritzemabosi

A. besseyi, a

Ditilenchus spp., For example D. dipsaci.

The invention also provides a method of controlling harmful arthropods or nematodes on plants by applying an effective amount of a compound of formula I to the plants or the environment in which they grow.

For the control of arthropods or nematodes, the active ingredient is usually applied to sites infested by these pests at a dosage of about 0.1 kg to 25 kg of active ingredient per hectare of area treated. Under ideal conditions, depending on the pest being destroyed, lower doses may provide adequate protection. In contrast, in adverse weather conditions, in the control of resistant pests, and depending on other factors, higher doses of the active ingredient may be required. For foliar application, doses from 1 g to 1000 g / ha can be used.

In the case of soil insect control, the active ingredient-containing composition is uniformly distributed over the treatment area in any suitable manner. If desired, the entire field or field where the crop is grown may be treated, or the application may be carried out in close proximity to the seeds or plants to be protected. The active ingredient may be washed into the soil by spraying the treated area with water or left on the surface to flush it into the soil. During or after application, the composition may optionally

Even in the soil mechanically dispersed, for example, plowing or cultivator. The application can take place before, during sowing, after sowing but before emergence or after emergence.

The compounds of formula (I) may be applied in the form of solid or liquid formulations to the soil to control nematodes present in the soil, but they may also be applied to a leaf to control nematodes attacking aboveground parts of plants, such as the genera Aphelenchoides and Ditylenchus.

The compounds of formula I are capable of controlling pests eating parts of the plant remote from the site of application; for example, leaf-eating insects effectively destroy the substances applied to the roots.

In addition, the active compounds described can reduce the attack on plants by their insect repellent effects.

The compounds of formula (I) are very well suited to

S.::·;··./;.č V ·

· The protection of fields, meadows, plantations, greenhouses, orchards and vineyards, ornamental plants, park and forest trees. Examples of plants and crops that may be protected by these active substances include cereals (such as corn, wheat, rice and sorghum), cotton, tobacco, vegetables (such as beans, calerabas, cucumbers and pumpkins, lettuce, onions, tomatoes and peppers), field crops (such as potatoes, sugar beets, peanuts, soya, rape, sugar cane), forage meadows (such as maize, sorghum and lantern), plantations (such as tea, coffee, cocoa, banana) , oil palm, coconut tree, rubber tree, spices), orchards and groves (for example, with growth of stone fruit and pips, citrus, kiwi, avocado, mango, olives and walnuts), vineyards, ornamental plants, greenhouse, garden and park flowers and shrubs and forest trees (both deciduous and evergreen) in forests and kindergartens.

The compounds of the invention can also be used to protect wood and lumber (standing timber, harvested timber, sawn timber, stored timber, timber) against attack by sawflies (e.g., Urocerus) or beetles (e.g., from the Scolytidae family), Platypodidae, Lyctidae, Bostrychidae, Cerambycidae or Anobiidae or termites [such as Reticulitermes spp. (termites), Heterotermes spp. or Coptotermes].

Furthermore, the compounds of the invention can be used to protect stored products such as grain, fruit, nuts, spices and tobacco, whether unprocessed, ground or processed into various products, against attack by the needles, beetles and mites. Animal products such as leather, hair, hair and horsehair, wool and feathers in natural or processed form (for example, as carpets or textile products) may be protected against attack by pigs and beetles, as well as stored meat and fish against beetles, mites and flies.

The compounds of the formula I are very suitable for the control of arthropods, helminths or protozoa spreading or transmitting diseases to humans and animals, for example for controlling the abovementioned pests and in particular for controlling ticks, moths, lice, fleas, mosquitoes and midges and transmitting diseases. flies. The compounds of formula I are particularly useful for controlling arthropods, helminths or protozoa found in domestic animals as hosts or these pests feeding on the skin, skin or sucking blood of the aforementioned animals. For this purpose, the compounds described can be administered orally, parenterally, percutaneously or topically.

Coccidiosis, a disease caused by Eimeria spore infections, can cause considerable economic losses in domestic animals and birds, particularly in intensive breeding. This disease may be affected by cattle, sheep, pigs and rabbits, but the disease is particularly serious in poultry, especially in chickens.

Said poultry disease is generally spread by birds that have been infected by an infectious organism found in faeces, in contaminated litter or soil, or in feed or water jets. The disease is manifested by bleeding, accumulation of blood in the appendix or small intestine, penetration of blood into the faeces, general weakness and digestive problems. The disease often results in the death of the animal, but even those birds that survive the severe disease have a significantly lower market value as a result of the infection.

Application of a small amount of a compound of formula I, preferably in combination with poultry feed, completely prevents or greatly reduces the incidence of coccidiosis. The compounds of the invention are active against both the cecal form (caused by Eimeria tenella) and the intestinal forms (essentially caused by Eimeria acervulina, Eimeria brunetti, Eimeria maxima and Eimeria necatrix).

The compounds of formula (I) also have an inhibitory effect on oocysts, since they significantly reduce the number and / or sporulation of oocysts already formed.

The compositions described below for topical application to humans or animals, or to protect stored products, household equipment and generally accessible areas and facilities, can also be applied alternatively to growing crop plants and growing areas and as seed dressings.

Suitable methods of administering the compounds of Formula I include:

in the case of persons or animals infected or exposed to arthropods, helminths or elements, parenteral, oral or topical application of a composition comprising an active substance exhibiting immediate and / or protracted action against arthropods, helminths or protozoa, for example adding the composition to food or feed or to a suitable pharmaceutical a composition intended for oral administration, in edible baits, livestock salt, feed supplements, watering preparations, sprays, baths, soaking preparations, dusts, ointments, shampoos, creams, waxes and self-controlling systems in the environment in general, or specific places where pests can hide, including stored products, wood and timber, household and industrial and residential equipment and rooms application by spraying, fogging, dusting, smoldering, waxing, painting, granulate or bait, dosing into waterways, wells, reservoirs and other running or stagnant water, domestic animals in feed for controlling fly larvae in their feces, for growing plants foliar application in the form of spray, dust, granulate, mist and foam, generally in the form of suspensions of finely comminuted and encapsulated compounds of the formula I, for the treatment of soil or roots in the form of liquid pouring, dusting, granulation, smoke and foam and for seed dressing in the form of liquid or powdered preparations.

The compounds of the formula I can be applied for the control of arthropods, helminths or protozoa in the form of any type of agents known in the art as suitable for indoor or outdoor application to vertebrates or for arthropod extermination in rooms and open spaces containing at least one active ingredient. a compound of formula I in combination with one or more compatible diluents or excipients suitable for the intended use of the composition. All of these compositions can be prepared by any method known in the art.

Compositions suitable for administration to vertebrates or humans include those suitable for oral, parenteral, percutaneous or topical administration.

Oral formulations comprise one or more compounds of Formula I in combination with pharmaceutically acceptable carriers or excipients and / or finished coatings and are prepared, for example, in the form of tablets, pills, capsules, pastes, gels, infusions, premedicated foods and feed, premedicated drinking water, premedicated feed supplements, slow release boluses or other slow release forms intended to remain in the gastrointestinal tract. All of these forms may contain the active ingredient in microcapsules or coated with coatings that are unstable in either an acid or alkaline environment or other pharmaceutically acceptable coatings. Feed premixes and concentrates containing the compounds of the invention may also be used, in particular for the preparation of a pre-medicated feed, water or other materials intended for animal consumption.

Formulations for parenteral administration include solutions, emulsions or suspensions of the active ingredient in any pharmaceutically acceptable vehicle and solid or semi-solid subcutaneous implants or pellets intended for sustained sustained release of the active ingredient. These preparations can be prepared and sterilized by any suitable method known in the art.

Formulations for percutaneous and topical application include sprays, dusts, infusions, baths, lotions, ointments, shampoos, creams or waxes and optional devices (e.g. ear tags) attached to animals to allow an overview of the local or systemic application of the formulation to killing arthropods.

Solid or liquid bait compositions suitable for killing arthropods consist of one or more compounds of Formula I and a carrier or diluent, which may contain an edible material or other substance that causes the arthropod to consume the composition.

Liquid formulations include water-miscible concentrates, emulsifiable concentrates, suspension concentrates, wettable or soluble powders containing one or more compounds of Formula I that can be used to treat substrates or sites infested or exposed to arthropod infestations, including rooms, closed or open storage areas or production, tanks, reservoirs or other equipment and running or standing water.

Solid homogeneous or heterogeneous compositions comprising one or more compounds of formula I, for example granules, pellets, briquettes or capsules, can be used to treat standing or running water for a certain period of time. Similar effects can be achieved either by continuous or discontinuous addition of the above-described dispersion concentrates to water.

Formulations in the form of aerosols and aqueous or non-aqueous solutions or dispersions suitable for application by spraying, misting and spraying using low or ultra-low volumes may also be used.

Suitable solid diluents which may be used to prepare the compositions for the application of the compounds of formula I include aluminum silicate, diatomaceous earth, maize husks, calcium phosphate, cork powder, activated carbon, magnesium silicate, clays such as kaolin, bentonite or attapulgite and water-soluble polymers. Said solid compositions may optionally contain one or more compatible wetting, dispersing, emulsifying or coloring agents which, when solid, may serve as a diluent.

The described solid compositions, which are generally in the form of dusts, granules or wettable powders, are usually prepared by impregnating solid diluents with solutions of the compounds of formula I in volatile solvents, followed by evaporation of the solvents and grinding the products thus obtained. pellets or briquettes, or by encapsulating the finely divided active ingredient in natural or synthetic polymers such as gelatin, synthetic resins and polyamides.

The wetting, dispersing and emulsifying agents which may be present in the compositions, in particular wettable powders, may be of the ionic or non-ionic type. These are, for example, sulphoricinoleate, quaternary ammonium derivatives or products based on condensates of ethylene oxide with nonyl and octylphenol or carboxylic acid esters with anhydrosorbitols, which have been solubilized by etherification of the free hydroxyl groups by condensation with ethylene oxide, or mixtures of these types of surfactants. The wettable powders may be mixed with water immediately prior to use to obtain suspensions suitable for application.

Liquid applicable compositions containing the compounds of formula (I) may be solutions, suspensions and emulsions of the compounds of formula (I), optionally encapsulated in natural or synthetic polymeric materials, which compositions may contain wetting, dispersing or emulsifying agents. These emulsions, suspensions and solutions may be prepared using aqueous, organic or aqueous-organic diluents such as acetophenone, isophorone, toluene, xylene, mineral, animal or vegetable oils and water-soluble polymers and mixtures of these diluents, which may contain wetting, dispersing or emulsifying agents of the ionic or non-ionic type or mixtures thereof, for example the surfactants described above. If desired, the active ingredient-containing emulsions of the formula I can be used in the form of self-emulsifiable concentrates containing the active substances dissolved in emulsifiers or in solvents containing emulsifiers compatible with the active substance. By simply incorporating these concentrates into water, ready-to-use compositions are obtained.

Compositions containing the active compounds of the formula I which are intended for application for the control of harmful arthropods, nematodes harmful to plants, helminths or protozoa may also contain synergists (for example piperonyl butoxide or sesamex), stabilizers, other insecticides, acaricides, nematicides, antelmintic agents. or anticoccidial agents, fungicides (whether for agricultural or veterinary use, such as benomyl or iprodione), bactericides, attractants or repellents for arthropods or vertebrates, pheromones, deodorants, flavoring agents, coloring agents and adjuvants such as trace substances elements. The above-mentioned additives are intended to improve the efficiency, durability, safety, possible consumption or spectrum of action, or to otherwise improve the function of the composition on the treated area or on the treated or treated animal.

Examples of other pesticidally active substances which may be present in the compositions of the invention or which may be used in addition to the compositions of the invention are: acephate, chlorpyrifos, demeton-S-methyl, disulfotone, ethoprophos, fenitrothion, malathion, monocrotophos, parathion, phosalone, pirimiphos-methyl, triazophos, cyfluthrin, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, permethrin, aldicarb, carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, teflubenzuron, dicofol, tetapone, endosulfan lind, cartos, ivermectin, milbemycins, thiophanate, trichlorfon, dichlorvos, diaveridine and dimetridazo ,.

Compositions intended for application to control harmful arthropods, nematodes harmful to plants, helminths or protozoa usually contain from 0.00001 to 95%, in particular from 0.0005 to 50,% by weight of one or more compounds of the formula I or of all active ingredients (i.e. compounds of formula I together with other arthropod toxicants and nematodes harmful to plants, anthelmintics, anticoccidial agents, synergists, trace elements or stabilizers). The particular compositions and their dosages are chosen by farmers, livestock farmers, physicians or veterinarians, pest control workers or other specialists to achieve the desired effect (s). Solid and liquid preparations for topical application to animals, wood and timber, stored products or household equipment generally contain from 0.00005 to 90%, in particular from 0.001 to 10% by weight of one or more compounds of the general formula I.

Solid and liquid compositions intended for oral or parenteral (including percutaneous) administration to animals normally contain 0.1 to 90% by weight of one or more compounds of Formula I. Pre-medicated feeds normally contain 0.001 to 3% by weight of one or more compounds. '·:

The concentrates and supplements to be mixed with feed normally contain 5 to 90%, preferably 5 to 50% by weight of one or more compounds of the formula I. Mineral cattle salts normally contain 0.1 to 10% by weight of one or more compounds of formula I.

Dusts and liquid compositions for application to cattle, persons, objects, rooms or open areas may contain from 0.0001 to 15%, in particular from 0.005 to 2.0% by weight of one or more compounds of formula I. Suitable concentrations of one or more compounds of formula Even in the treatment of water they are between 0.0001 ppm and 20 ppm, in particular between 0.001 ppm and 5.0 ppm. These concentrations can also be used therapeutically in fish farming, while always maintaining an appropriate duration of action. The edible baits may contain 0.01 to 5.0%, preferably 0.01 to 1.0% by weight of one or more compounds of formula (I).

For parenteral, oral, percutaneous or other administration to vertebrate, the doses used depend on the species, age and state of health of the vertebrate treated and on the nature and degree of infestation (whether actual or potential) of arthropods, helminths or elements. In the case of oral or parenteral administration, a single daily dose of from 0.1 to 100 mg, preferably 2.0 to 20.0 mg per kilogram of animal body weight or, in the case of prolonged medication, a daily dose of 0.01 to 20.0 is generally suitable. mg, preferably from 0.1 to 5.0 mg per kilogram of animal body weight. By using means or devices for sustained release or dosing of the active ingredient, the daily doses required for several months of administration can be combined and administered to the animals simultaneously.

The results of the tests against the arthropods of representative compounds of the invention are presented below.

Test 1

A liquid preparation is prepared containing the test compound in one or several different concentrations in 50% aqueous acetone.

(a) Efficacy test for Plutella xylostella and Phaedon cochleariae

Circular cut-outs of round leaf leaves are placed on agar in Petri dishes and infected with 10 test insect larvae (2nd instar for Plutella xylostella, 3rd instar for Phaedon cochleariae). Each treatment, consisting of spraying the preparation with a certain concentration of active ingredient, is carried out in four trays. The dishes are further stored in an air-conditioned chamber at 25 ° C. After 4-5 days, the plates are removed from the chamber and the larval mortality is determined. The observed data are compared with mortality in control plates treated with only 50% aqueous acetone.

(b) Efficacy test for Megoura viciae

Bean plants, grown in pots and pre-infested with a mixture of different stages of iceberg aphids are sprayed with the test composition in a laboratory rotary sprayer up to trickling. The treated plants were placed in a greenhouse for 2 days and then the aphid mortality was determined and compared to the aphid population of control plants treated with only 50% aqueous acetone. Each treatment is carried out four times. The results obtained are reported on a scale of 0 to 3, in which the individual values have the following meaning:

all aphids mftve several aphids alive most aphids alive no significant mortality

(c) Efficacy test for Spodoptera littoralis

Round bean leaf slices are placed on agar in Petri dishes and infested with 5 Spodoptera littoralis larvae (2nd instar). Each treatment, consisting of spraying a preparation with a certain concentration of the test substance, is repeated at four sites. After 2 days, live larvae are transferred to similar dishes containing untreated leaves

The dishes are further stored in an air-conditioned ° C. After 2 or 3 days, the plates are then removed from the chamber and the average mortality in% is determined by comparison with the control plates treated with 50% aqueous acetone alone.

on the agar layer. chamber with temperature

In the above-described Plutella xylostella larvae test, the following compounds of the invention are active, causing at least 65% mortality at a concentration of less than 500 ppm:

- 10, 12-23, 25-27, 31-57, 59-70, 76-79, 81-88, 90-92, 96, 101.

In the above-described test against all developmental stages of Megoura viciae, the following compounds of the present invention are active, where a degree of 7/12 is achieved when applied at a concentration of 50 ppm:

11, 58, 71, 72, 73, 74, 75.

In the above-described Phaedon cochleariae larvae test, the following compounds of the invention are effective, causing at least 90% mortality at a concentration of less than 5 ppm:

24, 29, 80, 89.

In the above-described Spodoptera littoralis larvae test, the following compounds of the invention are active which, at a concentration of less than 500 ppm, cause at least 70% mor32 of talite: 28,30.

The following regulations illustrate the composition and preparation of compositions for use in the control of arthropods, namatodes harmful to plants, helminths or harmful elements containing as active ingredient a compound or compounds of formula I. The compositions described in Regulations 1 to 6 may conveniently be diluted with water to spray preparations suitable concentration of the active ingredient for use in agriculture.

Regulation 1

Water-soluble concentrate

Ingredients:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole 7% (w / v)

Ethylan BCP 10% (w / v)

N-methylpyrrolidone up to 100% by volume

Preparation:

Ethyl BCP is dissolved in a portion of N-methylpyrrolidone, the active ingredient is added and the mixture is heated with stirring until dissolved. The volume of the resulting solution was adjusted by adding the remaining solvent.

Regulation 2

Emulsifiable concentrate

Ingredients:

• - ··

5-amino-3-cyano-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

Soprophor BSU

Arylan CA

N-metylpyro1idon

Solvesso 150 to% (w / v) 4% (w / v) 4% (w / v)% (w / v) 100% v / v

Preparation:

Soprophor BSU, Arylan CA and the active ingredient are dissolved in N-methylpyrrolidone and the volume of the resulting solution is adjusted by adding Solvesso 150.

Regulation 3

Wettable powder,

Ingredients:

5-amino-3-cyano-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole

Arylan S

Darvan č. 2

Celite PF to% (w / w) 2% (w / w) 5% (w / w)

100% by weight

Preparation:

The above ingredients are mixed and ground in a hammer mill up to a particle size below 50 µm.

Regulation 4

Aqueous suspension concentrate

Ingredients:

5-amino-3-cyano-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoro-

methylthio 30% (W / v) Ethylan BCP 1% (W / v) Sopropon T36 0.2% (W / v) ethylene glycol 5% (W / v) Rhodigel 23 0.15% (W / v)

water up to 100% vol

Preparation:

The above ingredients are intimately mixed and milled in a ball mill up to a median particle size below 3 gm.

Regulation 5

Emulsifiable suspension concentrate

Ingredients:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole 30% (w / v)

Ethylan BCP 10% (w / v)

Bentone 38 0.5% (w / v)

Solvesso 150 to 100% vol

Preparation:

The above ingredients are mixed intimately and the mixture is ground in a ball mill up to a mean particle size below gm.

Regulation 6

Water dispersible granules

Ingredients:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole 30% (w / w)

Darvan č. 2 15% (w / w)

Arylan S 8% (w / w)

Celite PF up to 100% by weight

Preparation:

The above ingredients are mixed, micronized in a fluid mill and granulated on a rotary pelletizer by spraying with sufficient water (up to 10% w / w). The excess water in the resulting granules is dried in a fluid bed.

The following section provides a basic description of the commercial preparations used in previous regulations.

Ethylan BCP

Soprophor BSU

Arylan CA

Solvesso 150

Arylan S condensation product of nonylphenol with ethylene oxide condensation product of tristyrylphenol with ethylene oxide

70% (w / v) calcium dodecylbenzenesulfonate solution light aromatic solvent ( _C10 ) sodium dodecylbenzenesulfonate

Darvan sodium lignosulfonate

Celite PF

Sopropon T36 carrier based on synthetic magnesium silicate sodium polycarboxylic acid salt

Rhodigel 23 polysaccharide - xanthan

Bentone 38 an organic derivative of montmorillonite magnesium

Regulation 7

Dusts

Ingredients:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole 1 to 10% (w / w) bulk talc up to 100% by weight

The composition is prepared by thoroughly mixing the above ingredients. The powder composition may be applied to sites contaminated or susceptible to infestation by arthropods, such as various waste materials, stored products, household equipment or animals. Arthropods are destroyed after the arthropods have reviewed the product. The dusting can be applied to the desired sites, for example using mechanical sprayers, hand sprayers or devices that make the application self-acting at the instigation of the animal.

Regulation 8

Edible bait

Ingredients:

5-amino-3-cyano-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoro-

methylthio 0.1 to 1.0% (w / w) wheat flour 80% (w / w) molasses up to 100% by weight

The above bait composition, prepared by thoroughly mixing the above ingredients, may be distributed to locations infested with arthropods, such as ants, grasshoppers, cockroaches and flies, such as domestic and industrial rooms such as kitchens, hospital rooms or warehouses, or open to kill arthropods who eat this bait.

Regulation 9

solution

Ingredients:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole dimethylsulfoxide% (w / v) to 100% v / v

The above composition can be prepared by dissolving the pyrazole derivative in a portion of dimethylsulfoxide and bringing the solution with additional dimethylsulfoxide to the desired volume. The prepared solution can be applied percutaneously to pets infected with arthropods by the so-called. pour-on application or, after sterilization by filtration through a polytetrafluoroethylene membrane (pore size 0.22 A * m), by parenteral injection at a dose of

1.2 to 12 ml of solution per 100 kg animal body weight.

Prescription

Wettable powder

Ingredients:

5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole% (w / w)

Ethylate BCP (condensation product of nonylphenol with ethylene oxide containing 9 moles of ethylene oxide per mole of phenol) 5% (w / w)

Aerosil (ultra fine silica)

Celite PF (carrier based on synthetic magnesium silicate)% (w / w)% (w / w)

The above composition can be prepared by adsorbing Ethylan BCP onto Aerosil, mixing with the other ingredients, and comminuting in a hammer mill to a wettable powder that can be diluted with water to a pyrazole compound concentration of from 0.001% to 2% (w / v). volume) and applied to a site infested with arthropods, such as diptera larvae, or nematodes, by harmful plants, by spraying, or on domestic animals infected or exposed to arthropods, helminths or elements, spraying or bathing, or orally in drinking water, to control arthropods , helminths or protozoa.

Regulation 11

A delayed-release bolus can be prepared from a granule containing a thickener, a binder, a delayed release agent, and 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in varying percentages. substances. From the aforementioned mixtures, a bolus with a density of 2 or higher can be produced by compression and can be orally administered to ruminants. The bolus remains in the area between the bonnet and the rumen and continuously releases the pyrazole derivative continuously over a long period of time to control infestation of bred ruminants by arthropods, helminths or elements.

Regulation 12

From 0.5 to 25% (w / w) of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole and polyvinyl chloride base (up to 100% w / w) By mixing these components together with a suitable plasticizer, for example dioctyl phthalate, and treating the homogenous mixture by melt extrusion or hot pressing, a sustained release formulation in a suitable form, for example in the form of granules, pellets, briquettes or strips, can be prepared. For example, the composition may be dispensed into stagnant water or, in the case of a strip, may be adapted to a collar or ear tag for domestic animals to control insect pests with a pyrazole compound that is slowly released from the composition.

Similar compositions can be prepared by replacing 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in the above-mentioned regulations with an appropriate amount of any other compound of formula I.

The compounds of formula (I) may be prepared by the use or modification of known methods (i.e., methods previously used or described in the chemical literature). Generally, pyrazole ring formation is followed, if necessary, by modification or conversion of substituents.

It will be appreciated that in the following description of the various procedures, the different groups on the pyrazole ring may be introduced in a different order, and that in some cases appropriate protecting groups may need to be used, as will be apparent to those skilled in the art. The compounds of formula I can be converted into other compounds of formula I by known methods.

In the following, if the general symbols appearing in the formulas are not specifically defined, they are assumed to have the meanings given above, i. the meaning given for the first time to the symbol concerned. Unless otherwise indicated, the term "amino" or "amino" means unsubstituted amino.

Those compounds of formula I, wherein R ² is R ^a SO ₂ ^R SO, or R ^a with R ³ represents the unsubstituted amino group and R ¹ represents a cyano or acetyl group may be prepared by a process, and which is characterized in the compound of formula II ^C \ "C = NNHR ⁴

R / (II) in which

R6 is cyano or acetyl, reacted with a compound of formula

R ² CH CN 2 preferably with an equimolar amount of this material, usually in the presence of an anhydrous inert organic solvent, for example ethanol, and an equimolar amount of a base, for example sodium ethoxide, at a temperature of from 0 to 50 ° C.

Compounds of formula I wherein R ² is R 5 ^and R ³ is an amino group of the formula -NR ^e R ⁷ wherein

R @ ⁷ and R @ ⁷ each represent a hydrogen atom or a linear or branched alkyl, alkenylalkyl or alkynylalkyl group, as defined above, can be prepared according to process variant b '' according to the invention. According to this variant, the intermediate corresponding to general formula I, in which the place of R @ ³ is a hydrogen atom, with a compound of formula III

R ^with -SCl (III) wherein

R ^p is as defined above, in an inert organic solvent, preferably dichloromethane or chloroform, optionally in the presence of a base, preferably pyridine, at 0 to 50 ° C.

The compounds of formula I, wherein R ¹ is chloro or fluoro, R ² is a residue R ^a SO _a, R ^a SO or R ^S and R ³ is amino, can be prepared variant c of the process by which the compound of formula IV

R ^{2, x} c = c _k

NC Y (iv) in which

X and Y are both chlorine or fluorine, reacted with the phenylhydrazine of formula V

R 1 NHNH _and (V) wherein

R ⁴ is as defined above, or with an acid addition salt thereof, e.g. hydrochloride, in an inert solvent, preferably ether or tetrahydrofuran, and optionally in the presence of a base such as triethylamine or sodium acetate, at a temperature ranging from 0 ° C to a temperature refluxing the reaction solvent. When an acid addition salt of a compound of formula (V) is used, its reaction with a compound of formula (IV) is carried out in the presence of an alkali metal acetate, carbonate or bicarbonate, for example sodium or potassium.

In accordance with variant d (1), the compounds of formula I, wherein R ² is a radical R ^S, R ^x is a chlorine, bromine, iodine or fluorine atom or a cyano or nitro group and R ³ is amino, can also be prepared by reacting the corresponding 4-thiocyanatopyrazoles with organometallic reagents such as a compound of formula VI

R ^with -Mg-X ^x (VI) wherein

R ^p is as defined above and

X ^x represents a halogen atom, in an inert solvent such as diethyl ether or tetrahydrofuran, at a temperature from -78 ° C to the reflux temperature of the reaction mixture, or with a compound of formula IX

R ⁹ -C ⁸ Cl 1 * (IX) wherein R ⁹ -C = c ^- corresponds to the radical R ^s of formula I, in an inert solvent such as tetrahydrofuran or diethyl ether, at a temperature ranging from -78 ° C to room temperature.

Alternatively, in accordance with variant d (2), compounds of formula I wherein R ² is R ⁵ S as defined above except for 1-alkenylthio or 1-alkynylthio may also be prepared by reaction of an intermediate corresponding to formula I, in which the place of R @ ² is tiokyanatoskupina, with a base, preferably sodium hydroxide, or a reducing agent, preferably sodium borohydride, in the presence of a reagent of the formula VII

R ^s ' - X ² (VII) wherein

R ^p is as defined above for R ^{with the} exception of 1-alkenyl and 1-alkynyl and 'I

X ² represents a halogen atom, preferably bromine or iodine, preferably methyl iodide or propargyl bromide, or, as mentioned above, with a base, preferably sodium hydroxide, in the presence of an agent of formula VIIA

F _and C = C (Z) Z '(VIIA) wherein t

Z represents a fluorine, chlorine or bromine atom;

Z 'is as defined above for Z or is a trifluoromethyl group, in an inert organic or aqueous organic solvent such as methanol, ethanol, dioxane, or mixtures of these solvents with water, the reaction being carried out at a temperature of from

-40 ° C to reflux.

Alternatively, according to the version "a (3), those compounds of formula I, wherein R ⁵ S as defined above excluding 1-alkenylthio or 1-alkynylthio prepared by reductive alkylation of disulphides of general formula VIII

(VIII) using a reducing agent, preferably sodium dithionite or sodium borohydride, in the presence of a base, preferably sodium hydroxide or sodium carbonate, and a halide of the above formula VII, such as methyl iodide, in an inert organic or aqueous organic solvent such as ethanol or mixtures of alcohol and water, at a temperature ranging from room temperature to reflux.

According to a further variant e 'of the process according to the invention, those compounds of the formula I in which R ^z represents a radical R ³ SO or R 5 ^with SO _a may be prepared by oxidation of a sulfur atom in the corresponding alkylthio-, alkenylthio- or alinylthio compound wherein R ² is as defined above an R ^and S. This oxidation can be carried out using oxidizing agents of the formula X

R ¹⁰ -O-O-H (X) wherein

R ^xo represents a hydrogen atom, a trifluoroacetyl group or preferably a 3-chlorobenzoyl group, in a solvent such as dichloromethane or chloroform or trifluoroacetic acid, at a temperature of from 0 to 60 ° C, or by treatment with a potassium or potassium salt of Caroic acid in a solvent such as in methanol and water, at a temperature ranging from -30 ° C to 50 ° C.

According to another variant f (1) of the process according to the invention, those compounds of the formula I in which R ¹ represents a chlorine, bromine or iodine atom or a cyano or nitro group can be prepared by diazotization of an intermediate corresponding to the formula I R ^x is an amino group and R ³ is a hydrogen atom or an amino group, using sodium nitrite in a mineral acid, for example a mixture of concentrated sulfuric acid and acetic acid, at a temperature of 0 to 60 ° C, followed by reaction with cupric salt and mineral acid; with an aqueous solution of potassium iodide (when R @ ¹ is an iodine atom) at a temperature from 0 to 100, or with cuprous cyanide, or sodium nitrite in the presence of a copper salt in an inert solvent, for example water, at a pH of 1-7 and at a temperature of from 25 to 100 ° C. The diazotization may alternatively be carried out with an alkyl nitrite, for example tert-butyl nitrite, in the presence of a suitable halogenating agent, preferably bromoform or iodine or anhydrous copper chloride, at a temperature of from 0 to 100 ° C and optionally in the presence of an inert solvent, preferably acetonitrile or chloroform.

According to another variant * ^ (2) of the process, compounds of formula I, wherein R ¹ is F and R ³ is H or an amino group may be prepared by diazotisation of the corresponding amine in which the place of R @ ¹ is an amino group, using, for example, a solution of sodium nitrite in sulfuric acid and in the presence of fluoroboric acid or a salt thereof, followed by thermolysis or photolysis of the resulting diazonium fluoroborate by known methods.

According to another variant of the process of the invention, compounds of formula I wherein R ¹ is fluoro or cyano and R ³ is hydrogen or amino can be prepared by reacting a halide of formula I wherein R ^x is an atom chlorine or bromine, with an alkali metal fluoride, preferably with precision fluoride, or with a metal cyanide, preferably potassium cyanide, under anhydrous conditions in an inert solvent, preferably sulfolane, at a temperature ranging from room temperature to 150 ° C.

According to another variant h the method of the invention, the compounds of formula I, wherein R ¹ is nitro and R ² is a residue R ^a SO 2 or R ^a SO may be prepared by reacting an intermediate corresponding to general formula I, wherein R ¹ is an unsubstituted amino group and R ² is a radical R ^a SO 2, R ⁵ SO or R ^s and R ³ is H or an amino group with an oxidant, preferably trifluoroperacetic acid or m-chloroperbenzoic acid, in an inert solvent, preferably dichloromethane, at a from 0 ° C to reflux. Where R ² is a radical R ^{and an} S may occur in the reaction at the same time also the oxidation of the sulfur atom.

According to another variant of the method of the invention may be those of formula I, wherein R ^x is cyano and R ³ is H or an amino group, can also be prepared by dehydration of a compound corresponding to the formula I, in which in place of the symbol ^Rx is carbamoyl group. A compound of formula I in which a carbamoyl group is present in place of R ^x may be prepared by reacting a compound of formula I with a carboxyl group R ¹ , with a chlorinating agent, preferably thionyl chloride, at a temperature ranging from room temperature to at reflux, followed by reaction of the intermediate acid chloride with ammonia to give the intermediate amide. The above dehydration is generally carried out by heating with a dehydrating agent, for example phosphorus pentoxide or preferably phosphorus oxychloride, to a temperature of from 50 ° C to 250 ° C.

According to another variant of the process j, compounds of the formula I in which R ^x is

A 4Ί acetyl group and R ³ represents a hydrogen atom or an amino group, prepared by reaction of the corresponding nitrile of formula I wherein R ¹ is cyano or an ester of formula I wherein R ¹ is an alkoxycarbonyl group or carboxylic acids of formula I wherein R 1 ¹ represents a carboxyl group, with methyl lithium in an inert solvent, for example toluene, at a temperature ranging from -78 ° C to room temperature. Alternatively the nitrile of the formula I, wherein R ¹ is CN, or the corresponding ester, wherein R ^x represents an alkoxycarbonyl group. and react with a Grignard reagent of the formula CH ₃ MgX ³ , wherein X ³ is a halogen atom, preferably iodine, in an inert solvent such as diethyl ether or tetrahydrofuran at a temperature of from 0 ° C to the reflux temperature of the solvent.

In accordance with another variant of the process of the invention, compounds of formula I wherein R ¹ is acetyl and R ³ is as defined above may alternatively be prepared by oxidation of alcohols corresponding to formula I in which R ¹ is present 1-hydroxyethyl, by treating with an oxidizing agent, preferably pyridinium chlorochromate, in an inert solvent such as dichloromethane at a temperature ranging from 0 ° C to the reflux temperature of the solvent.

According to another variant of I '' of the process, compounds of formula I, wherein R ^x represents a formyl group and R ³ is as defined above, prepared by reacting the corresponding nitriles of the formula I, wherein R ¹ is CN, with (1 ) a suitable reducing agent, preferably diisobutylaluminum hydride, in an inert solvent, preferably tetrahydrofuran, at a temperature of from -78 ° C to room temperature, followed by mild hydrolysis with an acid, for example dilute hydrochloric acid, at room temperature, or with (2) Raney- nickel in formic acid, preferably with refluxing formic acid.

Variations of the 5-amino group are also within the scope of the invention and are collectively referred to as variant m. Compounds of formula I corresponding to formula IA

(IA) in which

R ⁶ represents a radical R ^{1 X} C (= O) -, wherein R ¹¹ represents a straight or branched alkyl or alkoxy group having 1 to 4 carbon atoms α '.

R ⁷ is hydrogen or a radical R ^{1: L} C (= O) - is identical to the radical R ^1X C (= O) - denoted by R ^6, or group ^{-NR6 R7} represents a cyclic imide as defined moiety may be prepared by reacting a compound of formula I in which R ³ represents an unsubstituted amino group, or an alkali metal salt thereof, with a compound of formula XI

R ¹¹ -CO-X * (XI) wherein

R ⁴ represents a chlorine or bromine atom, or with a compound of formula XII (R ^XX -CO) ₂ O (XII) or a dicarboxylic acid derivative. The reaction may be carried out in the presence or absence of an inert organic solvent such as acetonitrile, tetrahydrofuran, a ketone such as acetone, an aromatic hydrocarbon such as benzene or toluene, chloroform, dichloromethane or dimethylformamide and optionally in the presence of an acid binding agent such as pyridine, triethylamine or carbonate; an alkali metal bicarbonate such as sodium or potassium at a temperature ranging from 0 ° C to the reflux temperature of the reaction medium. Depending on the reaction conditions selected and / or the use of an excess of a compound of formula XI or XII, this yields a compound of formula IA in which R @ 8 represents a radical R @ ¹ C (= O) - wherein R @ ¹¹ is as defined above. and R ⁷ represents a hydrogen atom or a radical R ^{X 1} C (= O) -, or in which the group -NR ⁶ R ⁷ represents a cyclic imide radical as defined above.

Compounds of formula IA in which R ⁶ represents a formyl group and R ⁷ represents a hydrogen atom or a formyl group may be prepared by reacting a compound of formula I wherein R ³ represents an unsubstituted amino group with a mixed formic and acetic anhydride. This formyl acetic anhydride can be prepared from formic acid and acetic anhydride and its reaction with a compound of formula I can be carried out in the presence or absence of an inert organic solvent such as a ketone such as acetone or an aromatic hydrocarbon such as benzene or toluene and optionally in the presence of a reagent. an acid binding agent such as pyridine, triethylamine or an alkali metal carbonate or bicarbonate such as sodium or potassium at a temperature of from 0 ° C to the reflux temperature of the reaction mixture. In this way, depending on the reaction conditions selected and / or the use of excess formyl acetic anhydride, a compound of formula IA is obtained in which R ⁶ represents a formyl group and R ⁷ represents a hydrogen atom or a formyl group.

Compounds of formula (IA) in which R ^{@ 1} represents a formyl group or a radical R ^{@ 1} C (= O) - and R ^{@ 7} represents a hydrogen atom may be prepared by selective hydrolytic cleavage of the radical R ^{@ 1} C (= O) - or a formyl group. of formula IA, in which both R ⁶ and R ⁷ represent a radical R ^{1 X} C (= O) - or a formyl group. The hydrolysis is carried out under mild conditions, for example by treatment with an aqueous ethanolic solution or suspension of an alkali metal bicarbonate such as sodium or potassium, or aqueous ammonia.

The compounds of formula IA, wherein ^R is a straight chain or branched alkoxycarbonyl having 2 to 5 carbon atoms optionally substituted by one or more halogen atoms, and R @ ^-7 is H, may be prepared by reaction of a compound of formula IB

in which

R ¹³ represents an alkoxycarbonyl group of the formula R ^{X 3} C (= O), wherein R ¹³ represents a straight or branched alkoxy group having 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or a phenoxy group, with a compound of formula XIII

R ¹³ -H (XIII) wherein

R ^{X 3} is as defined above, to replace a first group represented by the symbol R ¹² by a hydrogen atom, and to replace the second group represented by R ^{X 2} alkoxycarbonyl group when R ¹² represents a phenoxycarbonyl group, or optionally to replace the second group represented by the symbol R ¹² by another alkoxycarbonyl in the case where R ^X2 in formula IB represents an alkoxycarbonyl group. It will be appreciated that the desired compound of formula IA is obtained by appropriate selection of the corresponding compounds of formulas IB and XIII. The reaction may be carried out in water or in an inert aqueous-organic or organic solvent, for example in a C 1 -C 4 alkanol such as ethanol or in an aromatic hydrocarbon such as benzene or toluene, or preferably in an excess of a compound of formula XIII, at a temperature ranging from room temperature to the reflux temperature of the reaction mixture and, if necessary, at elevated pressure, optionally in the presence of a base such as an alkali metal alkoxide such as an alkoxide derived from a compound of formula XIII.

Compounds of formula IA in which R ⁶ and R ⁷ , which may be the same or different, each represent a formyl group or a radical of formula R ^XX C (= O) -, may be prepared by reacting a derivative of a compound of formula IA wherein R ⁶ R ^{@ 10 is} C (= O) - as defined above or a formyl group and R @ ⁷ is hydrogen, with an alkali metal such as sodium or potassium, mixed formic anhydride or a compound of formula XI above. This reaction may be carried out in an inert aprotic solvent, for example dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the reaction mixture.

Derivatives of compounds of formula I wherein R ³ is unsubstituted amino, or formula IA wherein R ⁶ is R ^XX CO and R ⁷ is hydrogen, with an alkali metal, may be prepared in situ by reacting the corresponding compound with an alkali metal hydride , for example sodium or potassium, in an inert aprotic solvent, for example dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the reaction mixture.

Compounds of formula IB wherein R ¹² is R ^{X 3} C (= O) - may be prepared as described above. Intermediates of formula IB in which R ¹² is phenoxycarbonyl can be prepared by reacting a compound of formula I in which R ³ is an unsubstituted amino group with a compound of formula XIV

R ^X4 - CO - X ⁴ (XIV) in which

R ⁴ is phenoxy α

X ⁴ is as defined above, for example with phenyl 4-chloroformate, or with a compound of formula XV (R ⁴ -CO) ₂ O (XV) wherein:

R ¹⁴ is as defined above, using the conditions described above for the reaction of a compound of Formula I with a compound of Formula XI or XII.

Compounds of formula IA in which R ⁶ is a group R ^{x 5} representing a straight or branched alkyl alkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms and R ⁷ represents a hydrogen atom may be prepared by cleavage of R ^XX C (= O) - from a compound of the general formula of formula IA, wherein R ⁶ is R ^{x 5} and R ⁷ is R ^XX C (= O) -. The cleavage of the residue R ^XX C (= O) - can be carried out by selective hydrolysis under mild conditions, for example by treatment with an alkali metal hydroxide such as sodium or potassium in water or in an inert organic or aqueous-organic solvent such as a lower alkanol such as methanol, or a mixture of water and a lower alkanol, at a temperature ranging from room temperature to the reflux temperature of the reaction mixture.

Compounds of formula IA wherein R ⁶ is R ^x5 and R- ⁷ is R ^XX C (= O) - may be prepared by (1) reaction of a compound of formula IA wherein R ⁶ is hydrogen and R ⁷ means the radical R ^XX C (= O) -, or an alkali metal derivative thereof, for example sodium or potassium, with a compound of formula XVI

R ^xs - X ^with (XVI) in which

X ^a is Cl, Br or I, may be carried out in an inert solvent, such as dichloromethane, tetrahydrofuran or dimethyl formamide, at a temperature from room temperature to the boiling point of the reaction mixture under reflux and, using the compound of formula IA in the presence of a base such as Triton B, and (2) reacting a compound of formula IA, wherein ^R is H and R ⁷ is a radical R ^X, with a compound of the general formula XI or XII.

Compounds of formula I wherein R ³ is

The N- (alkyl, alkenylalkyl or alkynylalkyl) -N-formylamino group as defined above can be prepared by the process just described using mixed formic anhydride and acetic anhydride instead of compound XI or XII.

Those compounds of the formula IA, in which one or both R R® and ^R7 are a linear or branched chain alkyl, alkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms, the groups within R ⁶ and R ⁷ are identical, may be prepared by reaction of a compound of formula I wherein R ³ is an unsubstituted amino group, or an alkali metal derivative thereof such as sodium or potassium, with a compound of the above formula XVI, in the presence or absence of an inert organic solvent such as an aromatic hydrocarbon such as benzene or toluene; chloroform, dichloromethane, tetrahydrofuran or dimethylformamide and optionally in the presence of an acid binding agent such as pyridine, triethylamine or an alkali metal hydrogen carbonate such as sodium or potassium at a temperature ranging from 0 ° C to the reflux temperature of the reaction mixture. Icom.

According to another variant of the process according to the invention, the compounds of the formula I in which R ³ represents a straight or branched C 2 -C 5 alkoxymethylene amino group optionally substituted on the methylene group by a straight or branched C 1 -C 4 alkyl group, may be prepared by reacting a compound of formula I in which R ³ is an unsubstituted amino group with a trisalkoxyalkane in the presence of an acid catalyst such as p-toluenesulfonic acid at a temperature ranging from room temperature to the reflux temperature of the reaction mixture.

In accordance with another variant of the process of the invention, compounds of formula I wherein R ³ is -NHCH ₂ R ^xe wherein R ^xe is hydrogen or straight or branched (C 1 -C 4) alkyl may be prepared by reaction a compound of formula I wherein R ³ is -N = C (OR ^{X 7} ) R ^{X 6} wherein R ¹⁷ is a straight or branched (C 1 -C 4) alkyl group with a reducing agent, preferably sodium hydride. The reaction may be carried out in an inert organic solvent, preferably methanol or ethanol, at a temperature ranging from 0 ° C to the reflux temperature of the reaction mixture.

Compounds of formula I in which R ³ represents a halogen atom may be prepared by diazotization of the corresponding compound of formula I in which R ³ represents an amino group, using the procedure of variant f "used above for the preparation of compounds of formula I in which R ¹ represents a halogen atom. Fluorides of the formula I in which R ³ is a fluorine atom can be prepared by halogen exchange in halides of the formula I in which R ³ is a chlorine or bromine atom by the process of variant g used above for the preparation of compounds of the formula I, wherein R ¹ represents a fluorine atom.

According to another variant P of the process, compounds of formula I, wherein R ^x is formyl, acetyl, cyano or nitro, R ² is as above and R ³ is F, prepared by halogen exchange of a halide of of formula I wherein R ³ is a chlorine or bromine atom by heating with an alkali metal fluoride, preferably cesium fluoride, in an inert solvent, preferably sulfolane, at a temperature of from 50 to 150 ° C.

According to another variant q of the process according to the invention, compounds of formula I in which R ³ is hydrogen can be prepared by reacting a compound of formula I in which R ³ is amino with a diazotizing agent, preferably tert-butyl nitrite, in a solvent , preferably in tetrahydrofuran, at a temperature ranging from room temperature to reflux.

According to another variant of r process of the invention compounds of formula IA, wherein R ¹ represents cyano or nitro, R ² is a residue R ^a SO _=, and R ^E and R ⁱⁿ are straight or branched chain alkyl, alkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms, wherein R ⁷ may also be hydrogen, may be prepared by reacting a compound of formula I in which R ³ represents a halogen atom, preferably bromine, with the corresponding amine of formula R ⁶ R ⁷ NH or with dimethylhydrazine in the case of the two radicals R ^a and R ⁷ are methyl groups, in an inert solvent, preferably dioxane, tetrahydrofuran, N, N-dimethylformamide, dimethyl sulfoxide, or sulfolane, at a temperature from 25 to 100 ° C.

Intermediates of formula II in which R ^a is cyano or acetyl may be prepared by diazotization of aniline of formula

R ⁴ NH wherein

R ⁴ is as defined above,

generally using a solution of an equimolar amount of sodium nitrite in a mineral acid, for example a mixture of concentrated sulfuric acid and acetic acid, at a temperature of from 0 to 60 ° C, followed by reaction with a compound of the formula

CH ₃ COCH (C1) CN prepared according to the procedure described in J. Org. Chem. 43 (20), 3822 (1978), or with a compound of formula

CH ₃ COCH (C1) COCH ₃ in the presence of an inert solvent, for example a mixture of water and ethanol, optionally buffered, for example with an excess of sodium acetate, at a temperature of from 0 to 50 ° C.

Intermediates corresponding to formula I wherein R ³ is amino, R ² is replaced by hydrogen and R ^x is cyano may be prepared by diazotization of the aniline of the formula

R ⁴ NH wherein

R ⁴ is as defined above, usually by treating a solution of an equimolar amount of sodium nitrite in a mineral acid, for example a mixture of concentrated sulfuric acid and acetic acid, at a temperature of 0 to 60 ° C, followed by reaction with a compound of formula XVII

NC-CH ₂ -CH (R C 0 ^s) CN (XVII) wherein

R 1 is C 1 -C 6 alkoxy, preferably ethoxy or hydrogen, in the presence of an inert solvent, for example a mixture of water and ethanol, optionally in a buffer, for example sodium acetate, at a temperature of from 0 to 50 ° C. The following mild hydrolysis with a base such as aqueous sodium hydroxide, sodium carbonate or ammonia may be necessary to effect cyclization.

Used above intermediates of formula XVII, wherein R ¹ is H ®, they can also be used in the form of alkali metal enolates, which under acidic conditions prevailing in the above condensation reaction are converted to aldehydes.

Intermediates of formula I wherein R ¹ is as defined above except for the formyl group, on-site

R ² is a hydrogen atom and R ³ is an amino group, may be prepared by decarboxylation of a compound of formula I in which a carboxyl group is present in place of R ² , which is usually carried out by heating to a temperature of 100 to 250 ° C, optionally in the presence of an inert organic solvent, in particular Ν, Ν-dimethylaniline. Alternatively intermediates corresponding to general formula I, in which R ² replaced by hydrogen, R ¹ is as defined above other than a formyl group and R ³ is amino, prepared directly from esters of general formula I, wherein R ² is a radical - COOR wherein R is a straight or branched (C 1 -C 6) alkyl group by heating in an inert organic solvent, preferably acetic acid, to a temperature of from 50 ° C to reflux, in the presence of a strong acid, with preferably hydrobromic acid. If in the starting material, R ¹ is chloro or fluoro, may also be exchanged halogen to form intermediate compounds wherein R ² and R ³ are as above and R ¹ is bromo.

Intermediate carboxy compounds corresponding to general formula I, wherein R ¹ is as defined above other than the formyl group, at R ² is carboxy and R ³ is amino may be prepared by hydrolysis of esters in which the place of R @ ² is the above -COOR group, preferably by treatment with an alkali metal hydroxide in a solvent such as aqueous alcohol at a temperature of from 0 ° C to the reflux temperature of the reaction mixture.

Intermediate esters corresponding to general formula I, in which the place of R @ ² are as defined above, -COOR, R ³ is amino and R ¹ represents a cyano or acetyl group may be prepared in a manner analogous to that described above and variant "of the esters of of formula

ROOCCH CN st and intermediates of formula II, wherein R ® is cyano or acetyl.

Intermediate esters corresponding to formula (I) in which R @ ^{2 is} replaced by —COOR, R @ ³ is amino and R ^{@ 1} is chlorine or fluorine may be prepared by reacting phenylhydrazine of formula V with a compound of formula XVIII

ROOC X

C = C (XVIII)

NC Y in which

X, Y and R are as defined above, in a manner analogous to variant c described above.

Alternatively, intermediates corresponding to formula I wherein R ¹ is chlorine or fluorine, R ² is replaced by hydrogen, and R ³ is amino may be prepared by reaction of the corresponding aldehydes in which a formyl group is present at R ² , with an acid, preferably aqueous hydrochloric acid, in a solvent, preferably ethanol, at a temperature of from 50 ° C to reflux.

Intermediates corresponding to general formula I, in which the place of R @ ² is formyl, can be prepared by reaction of nitriles in which the symbol R ² replaced by a cyano group with a suitable reducing agent, preferably diisobutylaluminum hydride, in an inert solvent, preferably tetrahydrofuran uranium at -78 ° C to room temperature.

Intermediates corresponding to general formula I wherein the symbol R ² replaced by a cyano group may be prepared by reaction of a compound of formula XIX (XIX)

NC X \ / c = c

NC Y in which

X and Y are as defined above, i. dichlorodicyanethylene or difluorodicyanethylene, with the phenylhydrazine of formula (V) above, carried out in an analogous manner to that of variant c.

Intermediates of formula XX

(XX) in which

R ¹⁹ represents a radical R ² or a hydrogen atom and

R ³ represents a hydrogen atom or an amino group, may be prepared by a Curtius rearrangement of the acid azide of formula I, in which R ^{1 is} replaced by CON 3, or R ^{2 is} replaced by hydrogen and R ^{1 by} CONa, which is carried out by heating in an inert an organic solvent such as toluene to a temperature of from 50 to 150 ° C to form an isocyanate which is then reacted with, for example, tert-butanol to form a carbamate which is then hydrolyzed with dilute acid, preferably hydrochloric acid in ethanol, at a temperature ranging from room temperature to reflux.

Intermediate acid azides can be prepared by reacting a carboxylic acid of formula I wherein R ^{1 is} replaced by a carboxyl group and R ² and R ³ are as defined above, with an azide transfer agent such as diphenylphosphoryl azide in the presence of a base, with preferably triethylamine, in an inert solvent, preferably N, N-dimethylformamide, at a temperature of from 0 to 60 ° C.

Intermediate carboxylic acids having a carboxyl group at the R ¹ site may be prepared by hydrolysis of the corresponding esters having an alkoxycarbonyl group at the R ¹ site, for example, ethoxycarbonyl, using a base such as sodium hydroxide and a solvent, as an aqueous alcohol at a temperature of from 0 ° C to the reflux temperature of the solvent.

Intermediate esters of carboxylic acids in which R ^x represents an alkoxycarbonyl group and R ^x ® represents the radical R ² may be prepared by reaction of an intermediate of formula XXI

R \ COOR of ^{c =} % 6 (XXI)

NC X in which

R and R ² are as defined above, and

X * ⁵ represents a leaving group, such as a chlorine atom, with a phenylhydrazine of the above formula (VI), using a procedure analogous to variant c.

Intermediate esters of carboxylic acids in which

R ^x is as defined above, an alkoxycarbonyl group and the symbol R ² is replaced by the radical R ^{X 3,} can be alternatively prepared by a process analogous to the alternative of a reaction of a compound of formula II in which the symbol R ^and replaced by -COOR, wherein R is as defined above , with a compound of formula

R ^{X 9} CH CN 2 wherein

R ^xs is as defined above.

Intermediates corresponding to the general formula II, in which the symbol R ^{8 is} replaced by the group -COOR, can be prepared from known compounds [for example from the compound of formula CH ₃ COCH (C1) COOR] by analogous to the procedure described above for the compounds of the formula II. wherein ^R is cyano or acetyl.

Intermediate halides of formula XXI in which X ⁶ is chlorine and R and R ² are as hereinbefore defined, may be prepared by reaction of the sodium or potassium salts thereof corresponding to general formula XXI in which X ⁶ represents a moiety -O- Na + or ^_ -0K * with a suitable chlorinating agent, preferably phosphorus oxychloride, optionally in the presence of an inert solvent, for example tetrahydrofuran, at a temperature from 0 ° C to the reflux temperature of the solvent.

Intermediate salts of formula XXI in which X ® is -O-Na * or -0 "K * may be prepared by methods described in the literature by reacting the active methylene derivative of the formula R ² CH ₂ CN with a dialkyl oxalate with, for example, diethyl oxalate, in the presence of a metal alkoxide such as sodium ethoxide in an inert solvent such as an alcohol such as ethanol at a temperature of from 25 ° C to the reflux temperature of the solvent.

Intermediates corresponding to general formula I in which the symbol R ^* replaced with 1-hydroxyethyl, can be prepared by reaction of aldehydes of the formula I, wherein R ¹ is formyl, and R ³ is H or an amino group, with a Grignard reagent, preferably with methylmagnesium , in an inert solvent such as ether or tetrahydrofuran at a temperature ranging from room temperature to the reflux temperature of the solvent.

Intermediate 4-thiocyanatopyrazoles corresponding to formula I wherein R ^{2 is} replaced by thiocyanato and R ³ is amino can be prepared by reacting a compound of formula I where R ^{2 is} replaced with a hydrogen atom with a thiocyanato introducing agent such as a salt an alkali metal thiocyanic acid or an ammonium salt (e.g. sodium thiocyanate) and bromine, in an inert organic solvent such as methanol, at a temperature of from 0 to 100 ° C.

Intermediate disulfides of formula VIII can be prepared by hydrolyzing thiocyanates wherein R ² is thiocyanato and R ¹ is chloro, bromo or fluoro, cyano or nitro, using hydrochloric acid in the presence of ethanol, or reduction with sodium borohydride in ethanol. Both of these reactions are carried out at a temperature ranging from room temperature to reflux. Alternatively, thiocyanates can be converted to compounds of formula VIII by treatment with a base, preferably aqueous sodium hydroxide, preferably under phase transfer conditions using chloroform as a cosolvent and in the presence of a phase transfer catalyst, for example triethylbenzylammonium chloride, at room temperature to 60 ° C.

Intermediate diaminoesters corresponding to general formula I, wherein R ^x and R ³ is amino and the symbol R ² as defined above is substituted by an ester group -COOR containing 2 to 7 carbon atoms, may be prepared by reaction of an appropriately substituted phenylhydrazine of the formula V with a salt of an alkyl dicyanoacetate XXII

ROOC-CH (CN) ₂ (XXII) wherein

R is as defined above, with an alkali metal, preferably potassium ethyl dicyanoacetate, using hydrochloric acid at a temperature ranging from room temperature to reflux. The alkyl salts of alkyl dicyanoacetates can be prepared by reacting the corresponding alkyl chloroformate with malononitrile in the presence of potassium hydroxide in tetrahydrofuran, at a temperature of from 0 to 100 ° C.

Intermediate diaminosulfonylpyrazoles corresponding to formula I wherein R ¹ and R ³ are amino and R ² is a sulfonyl group of formula R ^with SO ₂ may be prepared by a procedure analogous to that just described by reacting a phenylhydrazine of formula V with a suitable alkylsulfonylmalononitrile salt of formula XXIII

R ^a SO ₂ -CH (CN) ₌ (XXIII) wherein

R ^p is as defined above, with an alkali metal.

The preparation of compounds of formula XXIII is described in the literature.

Intermediate esters corresponding to the general formula

I in which R ¹ is chlorine, bromine or fluorine, or a nitro group, the symbol R ² is substituted by -COOR as defined above, and R ³ is amino, can be prepared by analogous variation of f "diazotizing compounds zodpo65 sponding to formula I, wherein amino is present in place of R ¹ .

Intermediate esters corresponding to the general formula I in which R ^{@ 1 is} replaced by the group -COOR as defined above, R @ ³ is replaced by hydrogen and R @ ³ is amino can also be prepared by reacting the phenylhydrazine of formula V with an alkali metal salt of formula XXIV

H COOR

C = C (XXIV)

NC O'M ⁺ in which

M represents sodium or potassium; and

R is as defined above.

The reaction is carried out in an acidic medium, generally in dilute sulfuric acid, optionally in the presence of a co-solvent, for example ethanol, at a temperature ranging from room temperature to the reflux temperature of the solvent.

The invention further provides intermediates of the general formula

XXV

(XXV) in which

R ³ 'has the same meaning as given above for R ³ or is hydrogen, thiocyanato, formyl, cyano, carboxyl, straight or branched (C 2 -C 7) alkoxycarbonyl or dithio (which connects two pyrazole rings, such as for example in the general formula of villas)

R ³ 'is as defined above for R ³ or is diphenoxycarbonylamino and

R ¹ 'is as defined for R ¹ or represents an amino, 1-hydroxyethyl, carboxyl, carbamoyl or straight or branched C 2 -C 7 alkoxycarbonyl or alkoxycarbonylamino group, useful for the preparation of compounds of formula I, except for compounds of formula I And those compounds of formula XXV wherein R ⁴ is 2,6-dichloro-4-trifluoromethylphenyl, R ² 'is cyano, R ¹ ' is cyano and R ³ 'is amino, acetamido, dichloroacetamido, tert-butylcarbonylamino , propionamido, pentánamidoskupinu, bis (etoxykarbony1) amino, ethoxycarbonylamino, methylamino or ethylamino, or R ¹ 'is Cl and R ^3' is amino, terc.butylkarbonylaminoskupinu, bis (ethoxycarbonyl) amino or ethoxycarbonylamino, or ^R1 '= Br or yoga du, amino or ethoxycarbonyl and R ³ 'is amino or R ^x ' is fluorine and R ³ 'is hydrogen or amino, or R ¹ ' is nitro, amino, tert-butoxycarbonylamino or ethoxycarbonyl and R ³ 'is hydrogen atom, or wherein R ⁴ represents 2,4,6-trichlorophenyl, 2-chloro-4-trifluoromethylphenyl or 2,6-dichloro-4-trifluoromethoxyphenyl, R ² 'represents cyano, R ^{X |} is cyano and R ³ 'is amino, or wherein R ⁴ is 2,6-dichloro-4-trifluoromethoxyphenyl, R ² ' is cyano, R ¹ 'is chloro and R ³ ' is amino, or wherein R ⁴ R ^{2 '} represents a methanesulfonyl group, R ¹ ' represents a carboxyl group, a carbamoyl group or an ethoxycarbonyl group and R ³ 'represents an amino group.

A preferred intermediate is 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole.

The following examples and reference examples illustrate the invention but are not intended to limit the scope of the invention in any way. Unless otherwise stated, chromatography on silica gel (40/60 flash silica, May and Baker Ltd) is carried out at a pressure of 6.8 Pa.

Example 1

Compounds No. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

15, 90

To a solution of 20.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole in 100 ml of dichloromethane is added dropwise a solution of 10.8 g of trifluoromethylsulfenyl chloride in 50 ml under magnetic stirring for 1 hour. The resulting solution was stirred at room temperature overnight, then washed with 100 ml of water, dried over anhydrous magnesium sulphate and evaporated in vacuo to give 26.3 g of a solid which was recrystallized from toluene / hexane to give the title compound as a white solid. 24.2 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole as pale yellow-brown crystals, m.p. 169-171 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole with the substituted pyrazoles below, using trifluoromethylsulfenyl chloride, unless otherwise stated, yields the following compounds:

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) pyrazole 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylthiopyrazole in the form of pale yellow crystals, m.p. 125-126 ° C, from 5-amino-3-cyano-1- (2,6-dichloro-4-difluoromethoxyphenyl) pyrazole 5-amino-3-cyano-1- (2,6-dichloro) -4-difluoromethoxyphenyl) -4-trifluoromethylthiopyrazole as a yellow-brown solid, m.p. 127 DEG-128.5 DEG C., from 5-amino-1- (2-chloro-4-trifluoromethylphenyl) -3-cyanopyrazole 5- amino-1- (2-chloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole as a brownish solid, m.p. 142-144 ° C, from 5-amino-3-cyano-1- (2,4 6-Trichlorophenyl) pyrazole 5-amino-3-cyano-1- (2,4,6-trichlorophenyl) -4-trifluoromethylthiopyrazole as brown crystals, m.p. 192-193 ° C, from 5-amino-3-cyano 5-Amino-3-cyano-1- (2,6-dibromo-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole -1- (2,6-dibromo-4-trifluoromethylphenyl) pyrazole as an orange colorless crystals, m.p. 202-204 ° C, from 5-amino-1- (2-bromo-4-trifluoromethylphenyl) -3-cyanopyrazole 5-amino-1- (2-bromo-4-trifluoromethylphenyl) -3-cyano -4-Trifluoromethylthiopyrazole as a pale yellow solid, m.p.

M.p. 136-138 ° C, j

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and difluoromethylsulfenyl chloride 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-difluoromethylthiopyrazole m.p. 159-161 ° C, from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and 5-amino-3-cyano-1- (heptafluoropropylsulfenyl chloride) heptafluoropropylsulfenyl chloride. (2,6-Dichloro-4-trifluoromethyl-phenyl) -4-heptafluoropropyl-thiopyrazole resulting from flash chromatography on a silica gel dry column using dichloromethane / petroleum ether (2: 1) as a yellow solid, m.p. 148-150 ° C. , from 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-cyanopyrazole using tetrahydrofuran as solvent 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) - 183-185 ° C, from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and trichloromethyl 3-cyano-4-trifluoromethylthiopyrazole in the form of yellow crystals. 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trichloromethylthiopyrazole resulting in purification by chromatography as a white solid, m.p. 245-247 ° C.

In analogy to the above procedures, substituting trifluoromethylsulfenyl chloride for dichlorofluoromethylsulfenyl chloride and adding an equimolar amount of pyridine to the reaction mixture after stirring overnight gives the following compound:

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole 5-amino-3-cyano-4-dichlorofluoromethylthio-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole The residue was purified by chromatography using equal parts of ether and hexane as a white solid, m.p. 178-180 ° C.

In an analogous manner, in the presence of an equimolar amount of pyridine in the reaction solution:

from 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole recrystallization from hexane as a white solid, m.p. 149-150.5 ° C, from 5-amino-3-bromo-5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole. 1- (2,6-Dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole resulting from recrystallization first from a mixture of hexane and ethyl acetate and then from a mixture of hexane and cyclohexane as a white solid, m.p. 154.5-156 ° C; from 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoropyrazole 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoro-4-trifluoromethylthiopyrazole as white mp 123-126 ° C;

using chlorodifluoromethylsulfenyl chloride as the starting material 1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole as a white solid, m.p. 167-168 ° C. The product was purified by high-resolution liquid chromatography using an irregular column (21.4 mm x 25 cm @ 8 µm) and a 3: 2 mixture of acetonitrile and water as eluent.

Reference example 1

The 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole used in the previous example was prepared as follows.

A suspension of nitrosyl sulfuric acid prepared from 7.0 g of sodium nitrite and 27.5 ml of concentrated sulfuric acid was diluted with 25 ml of acetic acid, cooled to 25 C, and ^E, with stirring, mechanical stirring thereto for 15 minutes at te71 fence 25 to 32 ° C dropwise a solution of 21.2 g of 2,6-dichloro-4-trifluoromethylaniline in 50 ml of acetic acid. The mixture was stirred at 55 ° C for 20 minutes and then poured into a solution of 14.0 g 2,3-dicyanopropionate in 60 ml acetic acid and 125 ml water while stirring at 10-20 ° C. After 15 minutes, 200 mL of water was added and the oil layer was separated. The aqueous solution is extracted three times with 70 ml of dichloromethane each time, the extracts are combined with an oil layer and washed with ammonia solution (to pH 9). The organic phase is stirred for 2 hours with 20 ml of ammonia, the dichloromethane layer is separated, washed once with 100 ml of water and once with 100 ml of 1N hydrochloric acid, dried over anhydrous magnesium sulphate and after filtration evaporated to a oily residue which crystallizes with toluene. and hexane gave 20.9 g of the title compound as brown crystals, m.p. 140-142 ° C.

In an analogous manner, the 2,6-dichloro-4-trifluoromethylaniline is replaced by the correspondingly substituted anilines listed below.

The following compounds are obtained by lines:

from 2,6-dichloro-4-trifluoromethoxyaniline 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) pyrazole as a pale-brown solid, m.p. 119-120.5 ° C; 6-dichloro-4-difluoromethoxyaniline 5-amino-3-cyano-1- (2,6-dichloro-4-difluoromethoxyphenyl) pyrazole by washing the dichloromethane solution of the primary product with saturated sodium carbonate solution. The above product is recrystallized from toluene as a yellow solid, m.p. 120.5-122.5 ° C;

from 2-chloro-4-trifluoromethylaniline 5-amino-1- (2-chloro-4-trifluoromethylphenyl) -3-cyanopyrazole as an orange crystalline substance, m.p. 133-135 ° C, from 2,4,6-trichloroaniline 5 amino-3-cyano-1- (2,4,6-trichlorophenyl) pyrazole as a pale brown solid, m.p. 155-156 ° C, from 2,6-dibromo-4-trifluoromethylaniline 5-amino-3-cyano 1- (2,6-dibromo-4-trifluoromethylphenyl) pyrazole as a crystalline yellow solid, m.p. 142-146 ° C, from 2-bromo-6-chloro-4-trifluoromethylaniline 5-amino-1- (2- bromo-6-chloro-4-trifluoromethylphenyl) -3-cyanopyrazole as a brown crystalline solid, m.p. 146-148 ° C, and from 2-bromo-4-trifluoromethylaniline 5-amino-1- (2-bromo-4-trifluoromethylphenyl) -3-Cyanopyrazole as a yellow crystalline solid, m.p. 159-162 ° C.

The 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole used in Example 1 was prepared as follows.

A mixture of 5.0 g of 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethoxycarbonylpyrazole and 75 ml of 6N hydrochloric acid in 75 ml of glacial acetic acid is heated under reflux for 24 hours. under reflux. After cooling, the reaction mixture was evaporated to a small volume, basified to pH 12 with 2N sodium hydroxide and extracted three times with 75 ml of diethyl ether each time. The ethereal extracts were combined and evaporated in vacuo to give a mixture of 5-amino- and 5-acetamidopyrazoles as a gummy yellow solid weighing 3.5 g. This solid is dissolved in a mixture of 30 ml of 6N hydrochloric acid and 60 ml of dioxane, the solution is refluxed for 48 hours, then the volatiles are evaporated in vacuo and the residue is purified by column chromatography using dichloromethane / hexane (4: 1). 1) as eluent. Evaporation of the eluate containing the main component yielded 1.3 g of the title compound as an off-white solid, mp 128-129 ° C.

The 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethoxycarbonylpyrazole used above is prepared as follows.

To a mixture of 50.0 g of 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethoxycarbonylpyrazole and 21.0 g of copper (II) chloride in 600 ml of acetonitrile was stirred and cooled to 0 ° C. 15.0 g of t-butyl nitrite are added dropwise over 10 minutes. The reaction mixture was stirred at 0 ° C for 2 hours, then at room temperature for 2 hours, then evaporated to small volume and poured into 1500 ml of 5N hydrochloric acid. The resulting solution was extracted three times with 600 ml of 2N hydrochloric acid each time, dried over anhydrous magnesium sulfate and evaporated to a brown tarry residue. This tar material was separated from the desired product by silica gel dry column chromatography using dichloromethane / hexane (4: 1) as eluent and the product was further purified by column chromatography using hexane with increasing portions of dichloromethane (60-80%) as eluent. . The solid was dried in vacuo giving 15.8 g of the title compound as an orange solid, mp 143-146.5 ° C.

The 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethoxycarbonylpyrazole used above is prepared as follows.

To a stirred suspension of 49 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine in 220 ml of 0.9N hydrochloric acid is added

35.2 g of ethyl dicyanoacetate potassium salt. The reaction mixture was heated under reflux for 18 hours, then cooled, the precipitated solid material was filtered off and dried after trituration with diethyl ether (250 ml). 56 g of an off-white solid are obtained, which, after recrystallization from ethyl acetate-hexane, yields 29.2 g of the title compound as an off-white solid, m.p. 196-197 ° C.

Ethyl dicyanoacetate potassium is prepared as follows.

To a stirred solution of 560 g of potassium hydroxide in 2.0 liters of water was added dropwise a solution of 520 g of ethyl chloroformate and 330 g of malononitrile in 500 ml of tetrahydrofuran over 1 hour while maintaining the temperature by external ice cooling below 40 ° C. The reaction mixture was stirred at room temperature for 1 hour, then cooled to 0 ° C, the precipitated solid material was filtered off and dried over phosphorus pentoxide. 334.4 g of the title compound is obtained as an off-white solid.

The 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole used in the above example was prepared as follows.

A mixture of 3.3 g of 5-amino-4-ethoxycarbonyl-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and 30 ml of 48% hydrobromic acid in 50 ml of glacial acetic acid is heated under reflux for 18 hours. under reflux. The reaction mixture was evaporated to a small volume, the residue basified with 1N sodium hydroxide solution, the product was filtered off and dried. 2.9 g of material are obtained, which after recrystallization from ethanol-water gives 2.5 g of the title compound as a colorless solid, m.p. 132.5-134 ° C.

*, »

The 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoropyrazole used in the above example was prepared as follows.

A mixture of 1.5 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoro-4-formylpyrazole, 40 ml of methanol and 10 ml of 2N hydrochloric acid is heated under reflux for 24 hours. condenser. After evaporation in vacuo, the residue was treated with 100 ml of water and extracted twice with 100 ml of ethyl acetate each time. The extract was washed with 50 ml of saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo.

Chromatographic purification using dichloromethane as eluent gave the title compound as a white solid, mp 128-129 ° C.

The above 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoro-4-formylpyrazole was prepared as follows.

To 2.2 g of 5-amino-4-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-fluoropyrazole (preparation is described in published PTC application WO 8703-781-A) dissolved in 40 ml of dry tetrahydrofuran, while stirring under nitrogen at -70 ° C, 13 ml of a 1M solution of diisobutylaluminum hydride in toluene are added. The mixture was allowed to warm to room temperature over 2 hours, then allowed to stand overnight, then poured into a mixture of 50 ml of 2N hydrochloric acid and 50 g of ice. After stirring for half an hour, 25 ml of toluene are added, the organic phase is separated and the aqueous layer is extracted twice more with 100 ml of dichloromethane each time. The combined organic solutions were washed with 20 ml of sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. 1.5 g of a brown solid are obtained which, after chromatographic purification using toluene / ethyl acetate (98: 2), affords 1.0 g of the title compound as a pale yellow solid, m.p. 137-139.5 ° C. .

'I · ¹

Example 2

Compounds No. 16 and 17

To a mixture of 1.15 g of anhydrous cupric chloride and 20 ml of acetonitrile was added 0.73 g of tert-butyl nitrite under stirring at 0 ° C. After 10 minutes at 0 ° C, a solution of 3.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 5 ml of acetonitrile was added and the resulting mixture was stirred first 2 hours at 0 ° C and then at room temperature overnight. The reaction mixture was evaporated in vacuo and the residue was dissolved in a mixture of 50 ml of dichloromethane and 50 ml of 5M hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, evaporated in vacuo and the residue purified by chromatography using a mixture of petroleum ether (bp 60-80 ° C) and dichloromethane (2: 1) as eluent. Recrystallization from petroleum ether (b.p. 60-80 ° C) afforded 0.55 g of 5-chloro-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole as a white crystalline solid, m.p. mp 131-132 ° C.

The procedure is analogous to that starting from 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole, the reaction is carried out at 0 ° C for 2 hours and then the reaction mixture is heated to reflux. Purification by chromatography using dichloromethane as eluent followed by recrystallization from toluene / hexane gave 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole as a white solid mp 177-179 ° C.

Reference example 2

The 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole used in the previous example was prepared as follows.

To a mixture of 30.0 g of methanesulfonylmalononitrile hydrochloride and 150 ml of water, 11.7 g of potassium carbonate are added in portions with stirring, then 41.0 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine are added and the mixture is heated at room temperature overnight. Mp 100 ° C. After cooling, the yellow solid was filtered off, washed with water and recrystallized from aqueous methanol. After thorough washing with ether, 14.6 g of the title compound is obtained as a white solid, m.p. 224-226 ° C.

Example 3

Compounds No. 18, 19, 20, 99

To 19.0 ml of triethyl orthoformate, 4.0 g is added first

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole followed by 0.019 g of p-toluenesulfonic acid. The reaction mixture was heated at reflux for 21 hours, then cooled and the triethyl orthoformate was evaporated in vacuo. A brown oily residue is obtained which is purified by chromatography using a mixture of equal parts of dichloromethane and hexane as eluent. Evaporation of the eluates in vacuo gave 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-trifluoromethylthiopyrazole as a colorless solid, m.p. 70-71.5 ° C.

The procedure is analogous except that triethyl orthoacetate is used instead of triethyl orthoformate and toluene is used as solvent. There was thus obtained 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxyethylidenamino-4-trifluoromethylthiopyrazole as a pale yellow solid, m.p. 71-73 ° C.

The procedure is analogous except that 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole is replaced by 5-amino-3-cyano-1- (2,6- dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole using triethyl orthoformate and toluene. There was thus obtained 3-cyano-1- (2,6-dihydro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-methanesulfonylpyrazole as a cream solid, m.p. 145-147 ° C.

By analogy to 3-cyano-1- (2,6-dichloro-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulphonylpyrazole and triethyl orthoformate in the absence of toluene) was obtained in an analogous manner. (dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-trifluoromethylsulphonylpyrazole resulting from recrystallization from hexane as a white solid, m.p. 118.8-119.8 ° C.

Example 4

Compounds No. 21,22,23,24,96

To a stirred solution of 4.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole and 2.3 g of acetyl chloride in 40 ml of acetonitrile is added dropwise at 0 ° C at 78 ° C. 1.3 ml of pyridine. The resulting yellow solution was warmed to room temperature over 45 minutes, then heated at reflux for 24 hours, cooled and evaporated in vacuo. The residue is dissolved in 100 ml of dichloromethane, washed twice with 100 ml of water each time, dried over anhydrous magnesium sulfate and evaporated in vacuo. 4.2 g of a brownish-yellow solid are obtained which, after purification of dichloromethane as eluent by tallizing from toluene, yields 2.0 g of 5-acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole. as a colorless solid, m.p. 217 DEG-chromatography using and followed by &gt;

In analogy, the following two compounds are obtained by replacing acetyl chloride with propionyl chloride:

3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (propionyl) amino-4-trifluoromethylthiopyrazole as white crystals, m.p. 128-130 ° C; and

3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propionamido-4-trifluoromethylthiopyrazole as a pale yellow solid, m.p. 178.5-182 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole for 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) 4-Methanesulfonyl-pyrazole gives 5-acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-methanesulfonyl-pyrazole as a cream solid, m.p. 220-222 ° C.

The procedure was carried out in an analogous manner except that 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole was used as starting material. In this case, the reaction mixture was refluxed for 3 hours. There was thus obtained 5-acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole as a white solid, m.p. 208-211 ° C.

Example 5

Compounds No. 25, 26, 27, 28, 29, 30, 97

To a solution of 5.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 80 ml of dry tetrahydrofuran is added under stirring at room temperature under nitrogen at 0, 5 hours 0.36 g of an 80% oil dispersion of sodium hydride. After a further 0.5 hours, 2 drops of 15-crown-5 and then 1.6 g of trimethylacetyl chloride are added first, the mixture is refluxed for 24 hours, then an additional 0.15 g of sodium hydride and 0.8 g of trimethylacetyl chloride are added. and the resulting mixture was refluxed for 18 hours. The reaction mixture was cooled, poured into 100 ml of water and extracted twice with 80 ml of ether each time. The ethereal extracts were dried over anhydrous magnesium sulphate and evaporated in vacuo to a yellow oil (6.2g) which was purified by chromatography using petroleum ether / dichloromethane (3: 2) as eluent to give 0.82g of 3-cyano- 1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthio-5-trimethylacetamidopyrazole as a white solid, m.p. 172.5-173.5 ° C.

In analogy to the replacement of trimethylacetyl chloride with the appropriate acylating agent,

using 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (methoxycarbonyl) amino-4-trifluoromethylthiopyrazole methyl chloroformate as a white solid, mp 135-136.5 ° C, using ethyl chloroformate and carrying out the reaction at room temperature with 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-trifluoromethylthiopyrazole as a white solid, m.p. 83 2 to 85.5 ° C, using chloroacetyl chloride and after purification by chromatography and recrystallization from toluene / hexane 5-chloroacetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 175-176 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole for 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -trifluoromethylphenyl) -4-methanesulfonylpyrazole and using the appropriate acylating agent, the following compounds are obtained:

using 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-methanesulfonylpyrazole ethyl chloroformate as a white solid, m.p. 195-198 ° C. using 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonyl-5-trimethylacetamidopyrazole trimethylacetyl chloride as a white solid, mp 245-247 ° C.

In an analogous manner, 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfonylpyrazole and ethyl chloroformate gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylphenyl (5-Bis (ethoxycarbonyl) amino-4-trifluoromethylsulfonylpyrazole), recrystallized from toluene / hexane as a white solid, m.p. 116-116.9 ° C.

Example 6

Compounds No. 31, 32, 33, 34, 35, 36, 93

To a mixture of 0.71 g of an 80% oil dispersion of sodium hydride and 30 ml of dry tetrahydrofuran was added 4.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole. After 20 minutes, 3 drops of 15-crown-5 are added, the mixture is cooled to 0 ° C, 3.4 g of methyl iodide is added, and the reaction mixture is stirred at 0 ° C for 0.5 hour and then at room temperature overnight. room temperature. The solvent was evaporated in vacuo and the residue was partitioned between dichloromethane (80 ml) and water (80 ml). The organic phase is dried over anhydrous magnesium sulphate and evaporated in vacuo. 4.29 g of a pale yellow solid are obtained which, after purification by chromatography using a mixture of equal parts of dichloromethane and petroleum ether, gives

2.11 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino-4-trifluoromethylthiopyrazole as a white solid, m.p. 109.5-110.8 ° C.

The following compounds are prepared in an analogous manner by replacing methyl iodide with an appropriate alkyl halide:

using 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-isopropylamino-4-trifluoromethylthiopyrazole isopropyl iodide, which is purified by chromatography and recrystallized from toluene / hexane as a cream colored solid at temperature. mp 173-175 ° C;

3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propylamino-4-trifluoromethylthiopyrazole as a white solid, m.p. 162-163.5 ° C; and

3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dipropylamino-4-trifluoromethylthiopyrazole as a white solid, mp 72.5-73 ° C, both of which are finally prepared using propyl bromide and carrying out the reaction first at 0 ° C and then at 70 ° C, followed by 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (propargyl) amino-4-trifluoromethylthiopyrazole propargyl bromide after recrystallization from a mixture of toluene and hexane as a white solid, m.p. 86-89 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole for 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -trifluoromethylphenyl) -4-methanesulfonylpyrazole and using methyl iodide as the alkylating agent gives 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-methylamino-4-methanesulfonylpyrazole as a yellow solid, m.p. Mp 169-172 ° C.

By analogy to the substitution of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole, 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) 4-Trifluoromethylsulfinylpyrazole, using dioxane as solvent and refluxing for 5 hours affords 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino-4-trifluoromethylsulfinylpyrazole as a white solid, m.p. Mp 154-161 ° C.

Example 7

Compounds No. 37, 38, 39, 40, 41, 95

To a suspension of 43.8 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole in a mixture of 141 ml of bromoform and 63 ml of dry acetonitrile is added dropwise over 5 minutes. minutes 29.9 g of t-butyl nitrite and the mixture was heated at 60-70 ° C for 2.75 hours. After cooling to 25 ° C, an additional 29.9 g of t-butyl nitrite is added and heating is continued for 2 hours. Evaporation in vacuo gave a yellow, oily residue which was filtered off after trituration with hexane and recrystallized twice from toluene / hexane. 34.0 g of 5-bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole are obtained in the form of a yellow solid, m.p. 136-137 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole with the phenylpyrazoles listed below:

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole (acetonotril is not used as the co-solvent in this case) 5-bromo-3-cyano-1- (2, 6-di83-chloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole as a red-brown solid, m.p. 161.5-164 ° C, from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) 4-Methanesulfonylpyrazole 5-bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole as a white solid, m.p. 160.5-162 ° C, from 3.5 -diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole (preparation described in Reference Example 2), using chloroform as solvent and replacing bromoform with two equivalents of bromine 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole as a white solid, m.p. 193-195 ° C; and from 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole. 3-bromo- 1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole as white crystals, m.p. 178-180 ° C.

Analogously, 5-bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole was also obtained as a yellow solid, m.p. 147-148 ° C. In this case, the reaction is carried out at 52 ° C for 2 hours.

Reference example 3

The 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole used in the above example was prepared as follows:

To a solution of 6.4 g of 3-tert-butoxycarbonylamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole in 150 ml of ethanol is added 20 ml of 50% (v / v) hydrochloric acid and the resulting mixture Heat to reflux for 1 hour. The solvent was evaporated in vacuo, the residue was dissolved in dichloromethane, washed with sodium bicarbonate solution and water, dried over anhydrous magnesium sulfate, and evaporated in vacuo. Recrystallization from ethyl acetate / hexane gave the title compound (3.0 g) as white crystals, m.p. 222-223 ° C.

3-tert-butoxycarbonylamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole was prepared as follows:

A mixture of 9.4 g of 3-carboxy-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole, 70 ml of thionyl chloride and 3 drops of N, N-dimethylformamide was heated under reflux for 2 hours. The solvent was evaporated in vacuo, 20 ml dry toluene was added and the mixture was again evaporated in vacuo. The solid residue is dissolved in 60 ml of dry acetone and a solution of 2.1 g of sodium azide in 15 ml of water is added over 5 minutes while stirring and maintaining the temperature at 10-15 ° C. After 30 minutes, the reaction mixture is poured into 250 ml of water and extracted three times with 80 ml of dichloromethane each time. The combined extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo to a maximum of 40 ° C to give a slightly reddish-yellow solid.

The azide formed was dissolved in dry toluene (80 ml) and heated at reflux for 0.75 hours to release nitrogen. After cooling, 15 g of tert-butanol are added and the mixture is heated under reflux for 2 hours. The reaction mixture was then allowed to stand overnight at room temperature and evaporated in vacuo. 6.6 g of a semi-solid brown solid (9.2 g) were purified by chromatography on Merck 230-400 mesh (6.8 Pa) silica gel using dichloromethane / ethyl acetate (98: 2) as eluent to give 6.6 g of the title compound. in the title.

3-Carboxy-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole was prepared as follows:

A mixture of 14.0 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxy-85-carbonyl-4-methanesulfonylpyrazole and 300 ml of 80% sulfuric acid is heated to 80 ° C with stirring for 4 hours. The reaction mixture was allowed to stand at room temperature overnight, then poured into excess ice and the precipitated solid material was filtered off. This material was dissolved in ethyl acetate, washed with water, dried over anhydrous magnesium sulfate and evaporated. It will be obtained

11.1 g of the title compound as a red-brown solid, m.p. 215-216 ° C.

The 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole used above is prepared as follows:

To a solution of 17.1 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole in 130 ml of dry tetrahydrofuran is added 33 ml of tert. .butylnitritu. The mixture was heated under reflux for 1.5 hours, then the solvent was evaporated in vacuo and the residue was dissolved in dichloromethane. After washing the solution with water, drying over anhydrous magnesium sulfate and evaporation, a yellow solid is obtained which, after recrystallization from toluene / petroleum ether (b.p. 60-80 ° C), affords the title compound as yellow crystals, m.p. 183-185. C. The product yield is

15.2 g.

The 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole used above is prepared as follows:

To 20 ml of absolute ethanol, while cooling in ice water, 0.25 g of an 80% oil dispersion of sodium hydride is added first, followed by 0.99 g of methanesulfonylacetonitrile, the mixture is stirred for 0.5 hour, then a solution of 3.0 g of ethyl is added. - chloro (2,6-dichloro-4-trifluoromethylphenyl) hydrazonoacetate in 20 ml of absolute ethanol and stirring is continued for 5 hours. The yellow solid (2.55 g) is filtered off and recrystallized from ethanol to give the title compound. as a colorless solid, m.p. 255 ° C.

Ethyl chloro (2,6-dichloro-4-trifluoromethylphenyl) hydrazonoacetate was prepared as follows:

To 24 ml of concentrated sulfuric acid was added 3.04 g of sodium nitrite over 15 minutes with stirring at 30-50 ° C. The resulting solution was cooled to 20 ° C and added dropwise over 15 minutes while maintaining the temperature at 35-40 ° C.

9.2 g of 2,6-dichloro-4-trifluoromethylaniline in 90 ml of acetic acid. The resulting solution was cooled to + 10 ° C and added dropwise over 45 minutes to a solution of 54 g of anhydrous sodium acetate and 7.0 g of ethyl chloroacetoacetate in a mixture of 72 ml of water and 48 ml of ethanol while stirring and maintaining the temperature by cooling to 10 ° C. After reaction at room temperature for 1 hour, the mixture was diluted with water, filtered, and the solid material was dissolved in dichloromethane. The solution was dried over anhydrous magnesium sulfate and, after filtration, evaporated in vacuo to give 11.9 g of the title compound.

Of the title compound as a white solid, m.p. 96-98 ° C. .

Example 8

Compounds No. 42, 43, 44, 45

To a solution of 4.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole in 20 ml of dry tetrahydrofuran at room temperature is added 5.76 g of tert-butyl nitrite. . The reaction mixture was refluxed for 3 hours and then evaporated in vacuo to a yellow solid which was purified by chromatography using petroleum ether / dichloromethane (2: 1) as eluent to give 3.12 g of 3-cyano-1. - (2,6-Dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole as a white solid, mp 126.5-128 ° C.

By analogy to the substitution of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole by the phenylpyrazoles below, the following compounds are obtained:

From 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole in 149-151 ° C. The product is obtained after heating under reflux for 29 hours and subsequent purification by chromatography and recrystallization from toluene / hexane.

From 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylthiopyrazole, 3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4- is obtained. trifluoromethylthiopyrazole as a white solid, m.p. 64-65 ° C.

From 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole, 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) - 4-Methanesulfonylpyrazole as yellow crystals, m.p. 147-150 ° C.

. «· · · '. ¹ 'in'

Example 9

Compounds No. 46, 47, 48, 49, 50, 94

To a solution of 3.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 50 ml of chloroform was added 3.61 g of iodine under stirring at room temperature, followed by stirring at room temperature. , 43 g of t-butyl nitrite. After 0.5 h, the reaction mixture was heated at reflux for 2 h and allowed to stand overnight at room temperature. The solid material is filtered off, washed with 50 ml of dichloromethane, the filtrate is combined with the washing liquid and washed twice with 50 ml each of sodium thiosulphate solution and then with 50 ml of water. After drying over anhydrous magnesium sulfate, the solution was evaporated in vacuo to give 3.8 g of a yellow solid which was purified by chromatography using petroleum ether / dichloromethane (2: 1) as the eluent followed by recrystallization from toluene / hexane. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-iodo-4-trifluoromethylthiopyrazole as a white solid, m.p. 187.3-188.3 ^e C.

By analogy to the substitution of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole by the phenylpyrazoles below, the following compounds are obtained:

From 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole, 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) - 5-Iodo-4-trifluoromethylsulfonylpyrazole as a white solid, m.p. 180-181 ° C. In this case, the reaction mixture was heated to reflux for 24 hours.

From 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole, 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-iodo- 4-Methanesulfonylpyrazole as a brown solid, mp 226-227 ° C. In this case, the reaction mixture was heated to reflux for 4.5 hours. '

From 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole (preparation described in Reference Example 3), 1- (2,6-dichloro-4-trifluoromethylphenyl) - 3-Iodo-4-methanesulfonylpyrazole as a cream colored solid, m.p. 150-151 ° C.

From 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole, 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-iodo-4-trifluoromethylthiopyrazole was obtained as a white solid. mp 80-81.5 ° C. The reaction is carried out using dry acetonitrile as solvent, initially at a temperature of up to 5 ° C and then at room temperature for 0.5 hours.

In a similar manner, starting from 5-amino-3-cyano-1- (2,6-dichloro)

-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole gives 3

-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-iodo-4-trifluoromethylsulfinylpyrazole as a pale yellow solid, m.p. 165-166 ° C.

Reference example 4

The 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole used in the above example was prepared as follows:

To a solution of 3.45 g of 3-tert-butoxycarbonylamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 80 ml of dry acetonitrile is added dropwise 2.6 g of iodotrimethylsilane under nitrogen. The mixture was stirred for 45 minutes, then 10 ml of methanol was added and after a further 15 minutes the resulting solution was concentrated in vacuo. The dark gum residue is dissolved in 100 ml of dichloromethane, washed first with 50 ml of sodium sulfite solution and then with 50 ml of water, dried over anhydrous magnesium sulfate and the dichloromethane is evaporated. 2.6 g of the title compound is obtained as an off-white solid, m.p. 130-135 ° C.

The above-used 3-tert-butoxycarbonylamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole is prepared as follows:

5.6 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole-3-carboxylic acid are dissolved in 50 ml of dry Ν, Ν-dimethylformamide, 1.33 g of triethylamine are added and, after cooling to 5, ° C a solution of 3.63 g of diphenylphosphoryl azide in 20 ml of Ν, form-dimethylformamide is added. When the temperature of the reaction solution to return to room temperature, the solution was heated at 35 ^e C, at this temperature for 2.5 hours and then keeping the temperature below 40 ° C, concentrated in vacuo. A solution of 5 g of sodium chloride in 100 ml of water was added to the residue, and the resulting suspension was extracted three times with 100 ml of ether each time. The combined extracts were washed with 50 ml of water, dried over anhydrous magnesium sulfate and evaporated to give 5.4 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole-3-carboic acid azide. carboxylic Acid. A solution of this azide in 200 ml of dry toluene was stirred and refluxed for 1.5 hours, then 35 ml of tert-butanol was added and refluxing continued for 4 hours. After evaporation of the reaction mixture in vacuo, the residue was purified by chromatography using dichloromethane as eluent to give 3.3 g of the title compound as an off-white solid, mp 122-125 ° C.

1- (2,6-Dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole-3-carboxylic acid as used above is prepared as follows:

To a suspension of 6.8 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-trifluoromethylthiopyrazole in 70 ml of ethanol is added a solution of 1.73 g of sodium hydroxide in 50 ml of water and the reaction mixture is stirred at room temperature for 1 h. Heat to reflux for 5 hours. The solvent is evaporated under vacuum, 250 ml of water are added to the residue and the mixture is acidified to pH 1 with concentrated sulfuric acid. The product is filtered off, washed with 100 ml of water and dried in vacuo at 120 ° C. 5.7 g of the title compound is obtained as a gray-colored solid, m.p. 175-177 ° C.

The 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-trifluoromethylthiopyrazole used above was prepared as described in Example 8 using 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) 3-ethoxycarbonyl-4-trifluoromethylthiopyrazole instead of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole. The title compound resulted in an off-white solid, mp 125.5-126 ° C.

The 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-trifluoromethylthiopyrazole used above was prepared according to the procedure of Example 1 from 5-amino-1- (2,6-dichloro-4). (trifluoromethylphenyl) -3-ethoxycarbonylpyrazole. After chromatographic purification, the product is a white solid

mp 213-214 ° C.

5-Amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonylpyrazole was prepared as follows:

To a solution of 50.0 g of 3-cyano-2-hydroxyprop-2-enoic acid ethyl ester sodium (N. S. Vulfson et al., C.A.57: 16604d) in 500 ml of cold water is added 2N cold sulfuric acid up to pH 1 with stirring. The resulting solution was extracted twice with 400 ml of ether each time, the extract was washed with 200 ml of water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The yellow oil (29.4 g) is dissolved in 400 ml of ethanol, 51.1 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine are added and the mixture is refluxed. After cooling, the vacuum and the orange-colored solid residue were recrystallized from toluene / hexane. 40.2 g of the title compound is obtained as a pale-brown-brown solid, m.p. 179-181 ° C.

The mixture is heated to boiling under the reaction solution

Example 10

Compounds No. 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62

To a partial solution of 48.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 600 ml of chloroform, 61.4 g of m-chloroperbenzoic acid is added under mechanical stirring. . The mixture was refluxed under nitrogen for 3.5 hours, then cooled, an additional 12.3 g of m-chloroperbenzoic acid was added, and refluxing was continued for 1 hour. The cooled reaction mixture is diluted with 600 ml of ethyl acetate, washed twice with 250 ml of sodium dithionite solution each, then twice with 250 ml of sodium hydroxide solution each, and then once with 500 ml of water. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a pale brown-brown solid which, after recrystallization from toluene / hexane / ethyl acetate, afforded 37.0 g of 5-amino-3-cyano-1- ( 2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole as white crystals, m.p. 219-221.5 ° C.

To a stirred solution of 10.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 100 mL of dichloromethane is added 4.5 g of m-chloroperbenzoic acid, the mixture is stirred over After stirring overnight, an additional 1.6 g of m-chloroperbenzoic acid was added in two portions and the resulting mixture was allowed to stand for 2 days. The reaction mixture is diluted with 30 ml of ethyl acetate, washed successively with 50 ml of sodium sulfite solution, 50 ml of sodium carbonate solution and 50 ml of water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica gel using dichloromethane as eluent to give 6.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole as a white solid, m.p. , 5 to 201 C.

By analogy to the above phenylpyrazoles, each of the other phenylpyrazoles is replaced by the following:

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethanesulfonylpyrazole as a white solid, m.p. 210-211.5 ° C; and

5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylsulfinylpyrazole as a white solid, m.p. 179-180 ° C. Both of these compounds are prepared from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-trifluoromethylthiopyrazole using an appropriate amount of m-chloroperbenzoic acid;

from 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole (the reaction is carried out at 40-50 ° C for 20 hours) 3-cyano-1- (2,6-dichloro-4) trifluoromethylphenyl) -493

- trifluoromethylsulfinylpyrazole as a white solid, m.p. 142.5-144.2 ° C;

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (1-methylprop-2-ynylthio) pyrazole 5-amino-3-cyano-1- (2,6- dichloro-4-trifluoromethylphenyl) -4- (1-methylprop-2-ynylsulfinyl) pyrazole as a white solid, m.p.

137.2 ° C;

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4 - methylsulfinylpyrazole in the form of a pale yellow-brown crystalline solid, m.p. 176-177 ° C;

from 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-isopropylthiopyrazole 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- isopropylsulfinylpyrazole as a white solid, m.p. 187-188 ° C;

from 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- trifluoromethylsulfinylpyrazole as a white solid, m.p. 179-180 ° C;

from 5-amino-4-tert-butylthio-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole using 2 mol equivalents of m-chloroperbenzoic acid in chloroform and after reaction at room temperature for 5 hours at 5-amino- 4-tert-Butanesulfonyl-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole as a pale yellow solid, m.p. 183-184 ° C.

The following compounds were prepared in an analogous manner:

from 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole 5-amino-3-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- trifluoromethanesulfonylpyrazole as a white solid, mp 162-164 ° C;

from 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propylamino-4-trifluoromethylthiolpyrazole at room temperature 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-propylamino -4-trifluoromethanesulfonylpyrazole as a yellow solid, mp 49-65 ° C;

from 5-acetamido-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole using 2 mol equivalents of m-chloroperbenzoic acid after refluxing for 20 hours in chloroform 5-acetamido-3- Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole as a white solid, m.p.

175.9 ° C.

Example 11

Compounds No. 63, 64

I _t

To a mixture of 0.96 ml of 85% hydrogen peroxide and 20 ml of dichloromethane at 0-10 ° C was added dropwise 6.0 ml of trifluoroacetic anhydride with stirring over 15 minutes. The resulting mixture was heated at 20 ° C for 5 min, then a suspension of 2.0 g of 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole in 20 mL of dichloromethane was added over 5 min. The reaction solution was heated at reflux for 1 hour, then allowed to stand overnight at room temperature and poured into 100 ml of water. The organic layer was washed successively with 30 ml of sodium metabisulphite solution and 30 ml of sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was recrystallized from dichloromethane / toluene / hexane to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonyl-3-nitropyrazole as a white solid, mp 190-192 ° C.

In an analogous manner, 3,5-diamino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole is replaced by 3-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole. amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonyl-3-nitropyrazole as a cream colored solid, m.p. 190-192 ° C. The oxidation is carried out first at 0 ° C and then for 1.5 hours at room temperature. In this case, purification by chromatography using dichloromethane as eluent and recrystallization from toluene is required.

Example 12

Compound No. 65

To a mixture of 0.31 g of 85% hydrogen peroxide and 20 ml of dichloromethane was added dropwise 2.1 g of trifluoroacetic anhydride while stirring at -10 ° C. After 15 minutes, the resulting mixture was allowed to warm to room temperature, stirred for 15 minutes, re-cooled to 0 ° C, and a solution of 1.0 g of 3-amino-1- (2,6-dichloro-4-) was added. Trifluoromethylphenyl) -4-trifluoromethyl-11-pyrazole (preparation described in Reference Example 4) in 20 ml of dichloromethane and the resulting solution was allowed to warm to room temperature. After two hours an additional portion of trifluoroacetic acid (prepared in the same manner as above using 0.31 g of 85% hydrogen peroxide, 20 ml of dichloromethane and 2.1 g of trifluoroacetic anhydride) was added. The reaction mixture is stirred overnight, then poured into 50 ml of water and the dichloromethane layer is washed successively with 30 ml of 5% sodium sulfite solution, 30 ml of sodium bisulfite solution and 30 ml of water. The organic solution was dried over anhydrous magnesium sulfate and evaporated in vacuo. 0.8 g of green bituminous material is obtained which, after purification by chromatography with dichloromethane / hexane (3: 2) as eluent, yields 0.3 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3 -nitro-4-trifluoromethylsulfinylpyrazole as a pale green solid, m.p. 124-130 ° C.

Example

Compounds No. 66, 67

To 4.0 g of 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-carbamoyl-4-methanesulfonylpyrazole is added 20 ml of phosphorus oxychloride, the solution is heated at 50-60 for 3.25 hours. ° C and then allowed to stand overnight at room temperature. The reaction mixture is poured into 200 ml of water with vigorous stirring, the precipitated solid product is collected and dried under vacuum. Recrystallization from toluene-ethanol gave 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-cyano-4-methanesulfonylpyrazole as pale yellow-brown crystals, mp 235-238 ° C.

In an analogous manner to the above, substituting 5-amino-3-carbamoyl-1- (2,6-dichloro-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-carbamoyl-4-methylsulfonylpyrazole) 4-trifluoromethoxyphenyl) -4-methanesulfonylpyrazole gives 5-amino-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -3-cyano-4-methanesulfonylpyrazole as a white solid, m.p. 202.5-203; 5 ° C.

Reference example 5

The 5-amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-methanesulfonylpyrazole used above is prepared as follows:

To a suspension of 40.0 g of 5-amino-3-carboxy-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-methanesulfonylpyrazole in 160 ml of toluene is added 150 ml of thionyl chloride and the mixture is heated under reflux for 3 hours. under reflux. The resulting solution was evaporated in vacuo, toluene (100 ml) was added and the mixture was evaporated again. The remaining acid chloride was dissolved in 200 ml of tetrahydrofuran and this solution was added dropwise over 15 minutes to a stirred solution of ammonia (300 ml), the temperature of which was maintained by cooling to 5-10 ° C during the addition. The reaction mixture was allowed to stand overnight, then 250 mL of water was added and the resulting mixture was extracted three times with 100 mL of ethyl acetate each time. The extracts are combined, washed twice with 250 ml of water each time and, after drying over anhydrous magnesium sulfate, evaporated in vacuo. The solid residue (34.9 g) was recrystallized from ethyl acetate / hexane to give the title compound (19.3 g) as a white solid, mp 219-220 ° C.

By analogy to the substitution of 5-amino-3-carboxy-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-methanesulfonylpyrazole

5-Amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-carboxy-4-methanesulfonylpyrazole gives 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3- carbamoyl-4-methanesulfonylpyrazole as a gray-brown powder, m.p. 250-253 ° C.

The 5-amino-3-carboxy-1- (2,6-dichloro-4-trifluoromethoxyphenyl) -4-methanesulfonylpyrazole used above is prepared by the method used to prepare 3-carboxy-1- (2,6-dichloro-4-trifluoromethylphenyl) - However, 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole (Reference Example 3) is substituted for 5-amino-1- (2,6-dichloro-4-methanesulfonyl-pyrazole). dichloro-4-trifluoromethoxyphenyl) -3-ethoxycarbonyl-4-methanesulphonylpyrazole. The product is a white solid, m.p. 195-196 ° C.

The 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-carboxy-4-methanesulfonylpyrazole used above is prepared as follows:

8.0 g of 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole were refluxed for 3 hours with 75 ml of 48% hydrobromic acid in 75 ml. of acetic acid. The reaction mixture was allowed to cool overnight, then evaporated in vacuo and the residue triturated with aqueous sodium bicarbonate solution. After drying in vacuo, 6.6 g of the title compound is obtained as a gray powder, m.p. 130-133 ° C.

The 5-amino-1- (2,6-dichloro-4-trifluoromethoxy) xyphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole used above was prepared according to the procedure described in Reference Example 3 except that ethyl chlorine (2.6 -dichloro-4-trifluoromethylphenyl) hydrazonoacetate is replaced by ethyl chloro (2,6-dichloro-4-trifluoromethoxyphenyl) hydrazonoacetate. The product is a pale brown solid, m.p. 207 ° C.

From ethyl-chloro (2-bromo-6-chloro-4-trifluoromethylphenyl) hydrazonoacetate, 5-amino-1- (2-bromo-6-chloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4- is prepared analogously. methanesulfonylpyrazole, which resulted as a white solid, mp 255.5-256.5 ° C.

Ethyl chloro (2,6-dichloro-4-trifluoromethoxyphenyl) hydrazonoacetate, used above, was prepared as described in Reference Example 3 by replacing 2,6-dichloro-4-trifluoromethylaniline

2,6-dichloro-4-trifluoromethoxyaniline. The desired product is a brown solid, m.p. 55-58 ° C. · ',

In an analogous manner, 2-bromo-6-chloro-4-trifluoromethylaniline is prepared as above using ethyl chloro (2-bromo-6-chloro-4-trifluoromethylphenyl) hydrazone acetate, which results in a pale yellow-brown solid, m.p. 116.5. to 117.5 ° C.

Example 14

Compound No. 68

To a solution of sodium ethoxide prepared from 0.36 g of sodium and 50 ml of absolute ethanol at room temperature was added 1.88 g of methanesulfonylacetonitrile, stirred for 1 hour, then a solution of 5.0 g of 1-chlorine was added dropwise with stirring. 1- (2,6-dichloro-4-trifluoromethylphenyl) hydrazonopropan-2-one in 50 ml of ether. The reaction mixture is stirred overnight, then diluted with 100 ml of water and extracted three times with 50 ml of ether each time. The combined ethereal extracts were dried over anhydrous magnesium sulfate and evaporated in vacuo. Recrystallization from toluene / hexane gave a brown solid which yielded 2.56 g of 3-acetyl-5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole as a red-brown solid, m.p. 7 to

178.9 ° C.

The 1-chloro-1- (2,6-dichloro-4-trifluoromethylphenyl) hydrazonopropan-2-one used above was prepared as described in Reference Example 3, substituting 3-chloropentane-2,4- for ethyl chloroacetate. Dion. The product resulted as a pale brown solid which melted at 77-79 ° C after recrystallization from petroleum ether (bp 60-80 ° C).

Example 15

Compounds No. 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 100

To a solution of 3.1 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-thiocyanatopyrazole in 50 ml of methanol is added under stirring at -7 ° C under nitrogen. 25 ml of methyl iodide. A solution of 0.92 g of potassium hydroxide in 10 ml of water is then added dropwise over 10 minutes while maintaining the temperature below 0 ° C. The reaction mixture was stirred at room temperature for 3 hours, then neutralized by adding solid carbon dioxide in the pellets and 180 ml of water were added. The precipitated solid product is filtered off and recrystallized from toluene / hexane (2: 1). 1.94 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole are obtained in the form of a brown crystalline solid, m.p. 170-172 ° C.

In analogy to the above, the following compounds were prepared by replacing methyl iodide with the alkyl halides below:

using ethyl iodide and aqueous ethanol as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethylthiopyrazole as a yellow solid, mp 158-160 ° C;

using propyl bromide and aqueous dioxane as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-propylthiopyrazole as a pale brown solid, mp 123-124 ° C;

using isopropyl bromide and aqueous isopropyl alcohol as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-isopropylthiopyrazole as a pale brown solid, m.p. 168-169 ° C;

using 1-iodo-2-methylpropane and aqueous dioxane as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (2-methylpropylthio) pyrazole as pale brown m.p. 134-137 ° C;

using 2-iodobutane and aqueous dioxane as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (1-methylpropylthio) pyrazole as a pale brown solid with m.p. mp 152.5-154 ° C. The product is purified by silica gel dry column chromatography using a mixture of equal parts of hexane and diethyl ether as eluent;

using allyl bromide and aqueous dioxane as solvent gave 4-allythio-5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole as a pale brown solid, m.p. 140-141 ° C. The product is purified by chromatography using a mixture of equal parts of hexane and diethyl ether as the eluent followed by recrystallization from toluene;

using propargyl bromide and aqueous methanol as solvent gave 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (prop-2-ynylthio) pyrazole as a brown solid at temperature mp 161-163 ° C;

using 3-bromobut-1-yne and aqueous methanol as solvent for 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4- (1-methylprop-2-ynylthio) m.p. 134 DEG-135.6 DEG C. pyrazole as an off-white solid. The product is first purified by chromatography using a mixture of equal parts of diethyl ether and hexane as eluent and then recrystallization from toluene / hexane;

using methyl iodide and aqueous methanol as solvent gave 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole as a white solid, mp 117-119 ° C. The product is purified by chromatography using dichloromethane as eluent.

Analogously using 5-amino-4- (2-chloro-1,1,2-trifluoroethylthio) -3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole using chlorotrifluoroethylene and aqueous dioxane as solvent as a white solid, m.p. 116-118 ° C. The product is purified first by chromatography using dichloromethane as the eluent and then recrystallizing from toluene / hexane (3: 10).

Reference example 6

The 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-thiocyanatopyrazole used above is prepared as follows;

To a suspension of 4.99 g of potassium thiocyanate in 75 ml of methanol, with stirring at -78 ° C, 0.8 ml of bromine dissolved in 10 ml of methanol was added dropwise over 25 minutes. After a further 20 minutes, a solution of 5.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole in 50 ml of methanol is added over 30 minutes, the reaction mixture is first stirred at -78. The mixture was allowed to warm to room temperature over 3 hours and poured into 250 ml of water. The precipitated solid material is filtered off and, after washing with water, recrystallized from toluene / hexane. This gave 3.1 g of the title compound as a white solid, m.p. 179-182 ° C.

102

By analogy to the above reference example, substituting 5-amino-3-bromo-1- (2,6-dichloro-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole) 4-Trifluoromethylphenyl) pyrazole afforded 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-thiocyanatopyrazole as a white solid, which was purified by chromatography using dichloromethane as eluent. at 162-163.5 ° C.

Preparation of the above chloro-4-trifluoromethylphenyl) pyrazole Example 1.

5-amino-3-bromo-1- (2,6-di) is described in reference

Example 16

Compound No. 79

To a stirred solution of 5.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-thiocyanatopyrazole in 70 mL of dry diethyl ether is added dropwise at 0 ° C under nitrogen atmosphere 7.92 ml of a 2M solution of tert-butylmagnesium chloride in dry ether. The resulting solution was allowed to warm to room temperature, stirred for 3 hours, then 40 mL of water was added and the mixture was stirred for 15 minutes. The ether layer was separated, washed with 50 ml of water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The brown solid residue was purified by chromatography using dichloromethane / petroleum ether (3: 1) as eluent to give 2.62 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4 tert-butylthiopyrazole as a pale yellow solid, m.p. 196-198.5 ° C.

Example 17

Compounds No. 80, 81

To a solution of 2.0 g of 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole (preparation described in Example)

103

15) A solution of 1.66 g of potassium hydrogen sulfate was added rapidly at -25 ° C in 45 ml of methanol, followed immediately by 22 ml of water. The mixture was stirred at 0 ° C for 30 minutes, then 0.4 g of potassium hydrogen sulfate was added thereto, the resulting mixture was stirred at room temperature for 2.5 hours, then poured into 300 mL of water and 35 mL of saturated sodium bisulfite solution. . The aqueous mixture is extracted twice with 150 ml of dichloromethane each time, the extracts are washed twice with 50 ml of water each time, dried over anhydrous magnesium sulphate and evaporated in vacuo. The crude product was purified by chromatography using a 4: 1 mixture of dichloromethane and ethyl acetate as eluent. 0.9 g of 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylsulphinylpyrazole is obtained in the form of a white solid, m.p. 135-136 ° C.

In an analogous manner, substituting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthiopyrazole for 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylphenyl) -4-ethylthiopyrazole and using an appropriate amount of potassium hydrogen sulfate.

¹ gives 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-ethanesulfonylpyrazole as a yellow solid, m.p. 180-183 ° C. In this case, the mixture was allowed to react at room temperature for 20 hours and the title compound was obtained without chromatographic purification.

Example 18

Compound No. 82

To a solution of 1.7 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxymethyleneamino-4-trifluoromethylthiopyrazole in 30 ml of methanol was added portionwise with 1.08 g of sodium borohydride. The reaction solution was allowed to warm to room temperature and after an additional 7 hours poured into 200 ml of water. The mixture is extracted three times with 50 ml of dichloromethane each time, dried over anhydrous magnesium sulfate and evaporated in vacuo. The white solid (1.4 g) was purified by chromatography using dichloromethane / petroleum ether (4: 1) as eluent. 0.42 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-methylamino-4-trifluoromethylthiopyrazole is obtained in the form of a white solid, m.p. 208.5 DEG-209.5 DEG.

Example 19

Compound No. 83

To a solution of 1.0 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxycarbonylamino-4-trifluoromethylthiopyrazole in 20 ml of dry tetrahydrofuran is added 0.095 g of sodium hydride under stirring at 0-10 ° C. . The mixture was stirred at room temperature for 2.5 hours, then 0.6 g of methyl iodide was added dropwise while cooling to 0-10 ° C and the resulting mixture was stirred overnight. After addition of an additional 0.6 g of methyl iodide, stirring is continued for 8.5 hours, then the reaction mixture is poured into 100 ml of water and extracted twice with 50 ml of dichloromethane each time. The extracts were dried over anhydrous magnesium sulfate and evaporated in vacuo to give 0.81 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5- (N-ethoxycarbonyl-N-methyl) amino- 4-trifluoromethylthiopyrazole as a white solid, mp 86.2-88.5 ° C.

Example 20

Compound No. 84

A mixture of 3.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole and 15.0 g of trifluoroacetic anhydride in 25 ml of tetrahydrofuran is heated at reflux for 6 hours. under reflux. The reaction mixture was allowed to stand overnight, then evaporated in vacuo, dissolved in 50 ml of dichloromethane, washed with 50 ml of sodium bicarbonate solution and 40 ml of water, dried over anhydrous magnesium sulfate and evaporated in vacuo. 2.9 g of a brown-colored oily residue are obtained, which, after trituration with hexane, gives 1.86 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -51-5.

- trifluoroacetamido-4-trifluoromethylthiolpyrazole as a white solid, m.p. 138.2-139.8 ° C.

Example 21

Compounds No. 85, 98

To a solution of 1.8 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-trifluoromethylthiolpyrazole in 20 ml of ethanol is added 20 ml of saturated sodium hydrogen carbonate solution, The mixture was heated at reflux for 1.5 hours, then evaporated in vacuo. The yellow oily residue is partitioned between 70 ml of dichloromethane and 70 ml of water, the aqueous layer is extracted once more with 50 ml of dichloromethane, the organic phases are combined and, after drying over magnesium sulphate, evaporated in vacuo. Trituration with hexane gave 1.23 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-ethoxycarbonylamino-4-trifluoromethylthiolpyrazole as a white solid, m.p. 108.7-109.7 ° C. C.

In an analogous manner, 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) amino-4-trifluoromethylsulfonylpyrazole is prepared from 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-bis (ethoxycarbonyl) phenyl 5-ethoxycarbonylamino-4-trifluoromethylsulfonylpyrazole, which was purified by chromatography using a mixture of equal portions of dichloromethane and hexane as a white solid, mp 112.4-113 ° C.

Example 22

Compound No. 86

To a solution of 1.1 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (1-hydroxyethyl) -4-trifluoromethylthiolpyrazole in 40 ml of dichloromethane is added 0.62 g of pyridinium chlorochromate and the mixture is stirred overnight at room temperature. After addition of 50 ml of ether, the above mixture was filtered through diatomaceous earth and the filtrate was evaporated in vacuo. The brown solid was triturated with hexane, filtered and the filtrate evaporated in vacuo. The yellow solid residue was recrystallized from cyclohexane to give 0.4 g of 3-acetyl-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole as a yellow solid, mp 89-91 ° C.

Reference example 7

1- (2,6-Dichloro-4-trifluoromethylphenyl) -3- (1-hydroxyethyl) 4-trifluoromethylthiolpyrazole used in the above example was prepared as follows:

To a solution of 1.64 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-formyl-4-trifluoromethylthiolpyrazole in 20 ml of dry ether was added dropwise 1.35 ml of a 3M methylmagnesium iodide solution in ether over 5 minutes under nitrogen. . The resulting solution was refluxed for 1.5 hours, cooled, and an additional 0.2 mL of methylmagnesium iodide solution was added in the same manner as above. The reaction mixture is refluxed for 1 hour, then poured into excess ice and 100 ml of dilute hydrochloric acid and extracted twice with 50 ml of ether each time. The extract was washed with 50 ml of sodium bicarbonate solution and 50 ml of water, dried over anhydrous magnesium sulfate and evaporated in vacuo. 1.46 g of the title compound is obtained as a yellow oil.

Example 23

Compound No. 87

To a stirred solution of 2.03 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiolpyrazole in 20 mL dry tetrahydrofuran was added dropwise under nitrogen at -60 to -70 ° C over 10 minutes. 10 ml of a 1.0 M toluene solution of diiso107 butylaluminum hydride. The reaction solution was allowed to warm to room temperature over 3 hours, then cooled to -10 ° C overnight, then poured into a mixture of ice and 100 mL of 2N sulfuric acid. The resulting mixture was stirred for 0.5 hour and then extracted three times with 25 ml of dichloromethane each time. The extract was washed with 50 ml of water, dried over anhydrous magnesium sulphate and evaporated in vacuo. 1.8 g of a yellow oily residue are obtained which, after purification by chromatography using a mixture of equal parts of dichloromethane and hexane as eluent, yields 1.5 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-formyl- 4-trifluoromethylthiolpyrazole as a white solid, m.p. 79-81 ° C.

Example 24

Compound No. 88

A solution of 2.0 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in 50 ml of 90% formic acid is heated together with 2.0 g of Raney-nickel. The mixture was then cooled and, after the addition of an additional 2.0 g of Raney-nickel, was heated for an additional 5 hours. The reaction mixture is filtered, the filtrate is diluted with 250 ml of water and extracted four times with 50 ml of dichloromethane each time. The extract was washed twice with 50 ml of sodium hydrogen carbonate solution each time, dried over anhydrous magnesium sulfate and evaporated in vacuo. The solid residue (1.0 g) was purified by chromatography using dichloromethane as eluent. Subsequent recrystallization from toluene / hexane gave 0.05 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-formyl-4-trifluoromethylthiopyrazole as yellow crystals, m.p. 140-143 °. C.

Example 25

Compound No. 89

108

A mixture of 15 ml of dry sulfolane and 3.0 g of molecular sieves (4 x 10 ^-1θ ιη) is stirred with 2.4 g of cesium fluoride under nitrogen at 60 ° C for 0.5 hours, then 2.0 g are added. g of 5-bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethanesulfonylpyrazole, the resulting mixture was stirred at 60 ° C for 2 hours, then allowed to stand overnight at room temperature. temperature. The reaction mixture is diluted with 50 ml of ether, filtered, washed with 100 ml of water and the aqueous phase is extracted three more times with 50 ml of ether each time. The combined organic phases are washed four times with 50 ml of water each time, dried over anhydrous magnesium sulphate and evaporated in vacuo. The oily residue was purified by chromatography using ether / hexane (1: 4) as the eluent, followed by recrystallization from hexane to give 0.17 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) - 5-fluoro-4-trifluoromethanesulfonylpyrazole as a white solid, m.p. 95-98 ° C.

Example 26

Compound No. 92

To a solution of 5.0 g of pentafluoroethyl iodide in 30 ml of dry ether, while stirring at -78 ° C for 2.5 hours, is simultaneously added dropwise a solution of 0.02 mol of phenylmagnesium bromide in 20 ml of dry ether and a solution of 7.6 g of 5-amino. 3-Cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-thiocyanatopyrazole in 75 mL dry ether. The resulting mixture was allowed to warm to room temperature and after an additional half hour at 0 ° C, 15 mL of a 2M hydrochloric acid solution was added. The ether layer was dried over anhydrous magnesium sulfate and evaporated in vacuo. 8.8 g of a brown gum are obtained which, after purification by flash chromatography on a silica gel column (dry) using a mixture of equal parts of dichloromethane and petroleum ether, gives 5-amino-3-cyano-1- (2,6- dichloro-4-trifluoromethylphenyl) -4-pentafluoroethylthiopyrazole as a yellow solid, mp 134.5-136.5 ° C.

109

Example 27

Compound No. 101

To a solution of 1.5 g of 5-bromo-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfonylpyrazole in 20 ml of dioxane is added 0.62 g of 1,1-dimethylhydrazine The reaction mixture was heated at 60 ° C for 4.25 hours and poured into 20 mL of water. The aqueous layer is extracted twice with 50 ml of dichloromethane each time, the extract is combined with the dioxane layer, the organic phase is washed once with 50 ml of water and, after drying over anhydrous magnesium sulphate, evaporated in vacuo. 1.4 solids are obtained which, after purification by chromatography using a mixture of equal parts of dichloromethane and hexane as eluent, yields 0.35 g of 3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -5-dimethylamino- 4-trifluoromethylsulfonylpyrazole as a white solid, m.p. 178-179 ° C.

Example 28

Compounds No. 1 and 13 and the intermediate in Reference Example 4

To a solution of 2.23 g of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and 0.55 g of pyridine in 50 ml of chloroform is added dropwise over 20 minutes while stirring at 0 ° C. solution of 1.24 g of trifluoromethylsulfenyl chloride in 15 ml of chloroform. The mixture was stirred at 0 ° C for 3 hours and the solvent was evaporated in vacuo. The yellow solid, 3.1 g, is purified by chromatography on silica gel (Merck, 230-400 mesh, 0.7 kgcm ^-2 ) using a 3: 1 mixture of dichloromethane and petroleum ether (b.p. 40-60 ° C) as eluent. 2.33 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole are obtained in the form of a white solid, m.p. 169.5-170.5 ° C.

In analogy to the above procedure, substituting 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyanopyrazole with the phenylphenols described below for the following compounds:

from 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole 5-amino-3-bromo-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylthiopyrazole in the form of colorless solid, m.p. 154.5-156 ° C and from 5-amino-1- (2,6-dichloro-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonylpyrazole) ethyl ester 4-Trifluoromethylphenyl) -4-trifluoromethylthiopyrazole-3-carboxylic acid as a white solid, m.p. 213 DEG-215 DEG.

The 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonylpyrazole used in the above example was prepared as follows:

A solution of 50.0 g of 3-cyano-2-hydroxyprop-2-enoic acid ethyl ester in 500 ml of cold water is acidified with cold dilute sulfuric acid to pH 1 with stirring, then 50 g of sodium chloride are added thereto, and the mixture is extracted 200 ml of ether each time. The extract was washed with 50 ml of water, dried over anhydrous magnesium sulfate and evaporated. The yellow-colored liquid residue (30.2 g) was dissolved in 400 ml of ethanol and 52.5 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine was added rapidly with stirring. The reaction solution was heated at reflux overnight, then cooled and evaporated in vacuo. The solid orange-colored residue, after trituration with 300 ml of hexane, was filtered and recrystallized from toluene / hexane by clarification with activated charcoal to give 43.4 g of the title compound as pale yellow-brown crystals, m.p. 177-179 ° C.

Reference example 8

To a solution of 10.1 g of 2,6-dichloro-4-trifluoromethylphenylhydrazine in 50 ml of tetrahydrofuran was added 8.5 g of anhydrous potassium carbonate while stirring at room temperature. A solution of 11.0 g of 2-chloro-3-cyano-3- (1-methyl) ethylsulfonylprop-2-enoic acid ethyl ester in 100 ml of tetrahydrofuran is added dropwise at 0 ° C, the reaction mixture is stirred for 2 hours, then The mixture is filtered and the filtrate is evaporated to a brown oil which, after trituration with 100 ml of hexane, gives 11.7 g of an off-white solid. This material was heated to reflux in ethanol and the solution was cooled. 8.5 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4- (1-methyl) ethylsulfonylpyrazole are obtained in the form of white crystals, m.p. 255.5-256.5. C.

Reference example 9

The 2-chloro-3-cyano-3- (1-methyl) ethylsulfonylprop-2-enoic acid ethyl ester used above is prepared as follows:

To 28.5 g of phosphorus oxychloride was added 10.0 g of sodium 3-cyano-2-hydroxy-3- (1-methyl) ethylsulfonylprop-2-enoic acid ethyl ester with stirring at room temperature. After 3 hours, the mixture was heated at 50 ° C for 1 hour, then evaporated in vacuo. Toluene was added to the residue, and the mixture was re-evaporated to give the title compound as a brown oil.

The 3-cyano-2-hydroxy-3- (1-methyl) ethylsulfonylprop-2-enoic acid ethyl ester sodium salt is prepared as follows:

To a solution of sodium ethoxide, prepared from 4.0 g of sodium and 80 ml of ethanol, was added with stirring 24.5 g of 2-sulfonylacetonitrile. After complete dissolution of all solids, 24.8 g of diethyl oxalate was added (over 10 minutes), whereupon a heavy precipitate formed. The reaction mixture is refluxed for 1 hour, then the yellow solid is filtered off and, after washing with hexane, dried in a vacuum desiccator. 41.3 g of the title compound are obtained, m.p. 195-197.5 ° C.

112

Example

Compounds No. 59 and 52 and the intermediate for compound no. 52

The procedure is as described below, substituting the phenylpyrazole below for 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthio-3-trifluoromethylpyrazole. The following compounds are obtained:

from 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-trifluoromethylthiopyrazole 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4- trifluoromethylsulfinylpyrazole as an off-white solid, m.p. 210-214 ° C;

from 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-bromo-4-trifluoromethylthiopyrazole 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-bromo-4 -trifluoromethylsulfinylpyrazole as a white solid, mp 179-180 ° C;

from 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylthiopyrazole 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4 -trifluoromethylsulfinylpyrazole as a white solid, m.p. 203-203.5 ^e C.

To a solution of 1.0 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylthio-3-trifluoromethylpyrazole in 40 ml of chloroform was added portionwise at room temperature with 0.42 g of m acid. chloroperbenzoic. After stirring for six hours, the reaction solution was diluted with dichloromethane and washed successively with sodium sulfite solution, sodium hydroxide solution and water. The organic phase is dried over anhydrous magnesium sulphate and evaporated in vacuo to a yellow oily residue which is purified by chromatography on silica gel (Merck 230-400 mesh, 0.7 kg.cm ^-2 ) using dichloromethane / ethyl acetate (4: 1). ) as eluent. There was thus obtained 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methylsulfinyl-3-trifluoromethylpyrazole as a white solid melting on decomposition at temperature.

113

M.p. 142-145 ° C.

Reference example 10

3.57 g of 5-carbamoyl-4-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-trifluoromethylpyrazole, together with 2.82 g of phosphorus pentoxide, are heated to 200 ° C with stirring. After 3 hours, ice is added to the cooled reaction product and the mixture is extracted three times with 50 ml of dichloromethane each time. The organic solution was washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo to a solid residue which, after recrystallization from hexane, afforded 1.8 g of 1- (2,6-dichloro-4-trifluoromethylphenyl) -4,5-dicyanoate. -3-trifluoromethylpyrazole as white crystals, m.p. 80 ° C.

Analogous to the procedure above, substituting 5-amino-3-carbamyl-1- (2,6-dichloro-4-) for 5-carbamoyl-4-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-trifluoromethylpyrazole trifluoromethylphenyl) -4-methanesulphonylpyrazole give 5-amino-3-cyano-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulphonylpyrazole in the form of a white solid, mp 214 ^e C.

Reference example 11

The 5-carbamoyl-4-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) 3-trifluoromethylpyrazole used in the above reference example is prepared as follows:

To 30 ml of thionyl chloride was added 6.0 g of 5-carboxy-4-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-trifluoromethylpyrazole, and the solution was heated under reflux for 4 hours with stirring. the solvent was evaporated in vacuo. Toluene (30 ml) was added and the mixture was evaporated again. The resulting orange-colored oily material was dissolved in 10 mL dry ether and this solution was added dropwise to a stirred and ice-cooled ammonia solution (20 mL; density 0.88). The mixture is stirred overnight,

114 ml of water are then added thereto, and the resulting mixture is extracted three times with 50 ml of dichloromethane each time. The combined extracts were washed with water and, after drying over anhydrous magnesium sulfate, evaporated in vacuo. 7.0 g of white solid are obtained, which, after recrystallization from ethyl acetate / petroleum ether, yields 4.3 g of the title compound as white crystals, m.p. 180-181 ° C.

The 5-amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole used in Reference Example 10 above was prepared by the same procedure except that 5-carboxy-4-cyano- 1- (2,6-Dichloro-4-trifluoromethyl-phenyl) -3-trifluoromethyl-pyrazole uses 5-amino-3-carboxy-1- (2,6-dichloro-4-trifluoromethyl-phenyl) -4-methanesulfonyl-pyrazole. The desired product is obtained as an off-white solid, mp 223-224 ° C.

The 5-amino-3-carboxy-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-methanesulfonylpyrazole used above is prepared as follows:

To 80 ml of 80% sulfuric acid was added with stirring 8.15 g of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-ethoxycarbonyl-4-methanesulfonylpyrazole (see Reference Example 3) and the mixture was stirred for 5 minutes. heated to 100 ° C. After cooling, the reaction solution is poured over ice, the solid material is filtered off and dried over phosphorus pentoxide in a vacuum desiccator. Recrystallisation of this material from methanol-petroleum ether to give the above-mentioned desired product as a white solid of melting point 203-205 C. ^E

Claims (10)

N-phenylpyrazole derivatives of the general formula I (i) in which R ^x is cyano, nitro, halogen, acetyl or formyl, R ³ is a radical ^R SO__, R ^a SO or R ^a S in which R ^a represents straight or branched alkyl, alkenyl or alkynyl group having up to 4 carbon atoms, optionally substituted with at least one halogen atom, R ³ represents a hydrogen atom or an amino group of the formula - NR ⁶ R ⁷ where R ⁶ and R @ ^-7, which can be identical or different, are hydrogen, straight or branched chain alkyl, alkenylalkyl or alkynylalkyl group containing up to each 5 carbon atoms, a formyl group or a straight or branched alkanoyl of 2 to 5 carbon atoms, and optionally substituted by at least one halogen atom, or R @ ⁷ and R @ ^{7 taken} together with the nitrogen atom to which they are attached form a five or six membered cyclic imido group or in each case represent a straight or branched alkoxycarboxylic acid. 116 ° ('' ''): C-P'C: R ² represents a C 2 -C 5 bonyl group optionally substituted by at least one halogen atom, or R ³ represents a straight or branched C 2 -C 5 alkoxymethyleneamino group optionally substituted on the methylene moiety with a straight or branched C 1 -C 4 alkyl group, or is a halogen atom and R ⁴ represents a phenyl group substituted in the 2-position by a fluorine, chlorine, bromine or iodine atom, in the 4-position a straight or branched alkyl or alkoxy group having 1 to 4 carbon atoms, optionally substituted by at least one halogen atom or chlorine or 6 optionally substituted fluoro or iodine,, Otoi wherein R ¹ is CN, R ² represents methanesulphonyl, R ³ is amino and R ⁴ is 2,6-dichloro-4-trifluoromethylphenyl. bromine, and in the ru, chlorine, bromine position with the exception of the compound, v 2 ± Z ± ôéen to claim 1, wherein R ^x is as defined above other than the formyl group, and R ^2, R ³ and R ⁴ are as hereinbefore defined except that neither R ⁶ nor R as defined herein do not mean ^-7 alkenylalkyl or alkynylalkyl. iO & u / rzfy (d The compound of claim 1, wherein R ² is an alkylsulfonyl, alkylsulfinyl or alkylthio group having from 1 to 5 carbon atoms. R ⁴ represents a hydrogen atom, an amino group or a methylamino group, and R ^x represents a halogen atom, a cyano group or a nitro group; and R 4 represents a halogen atom, a cyano group or a nitro group; ⁴ is as defined above. ·,-;.··· IN-.;, 117 A compound according to claim 3, wherein R is a nitro group and the remainder is as defined above. ¹ means cyan-generic symbols have A compound according to any one of claims 1 to 4, wherein R ⁴ represents a phenyl group as defined above substituted by a trifluoromethyl or trifluoromethoxy group, R ² represents an optionally halogenated alkylsulfonyl, -sulfinyl or -thio group containing from 1 to 4 carbon atoms and the remaining general symbols are as defined above. Compound-1 according to claim 5, wherein R ² is trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl and the remaining general symbols have the meanings given above. r & a - R ⁴ in / D & u, / 2 ^ Ty Ί. A compound according to any one of claims 1 to 6, wherein 2,4,6-trichloro, 2,6-dichloro-4-difluoromethoxy-, 2-chloro-4-trifluoromethyl-, 2-bromo-6-chloro-4- trifluoromethyl, The 2,6-dibromo-4-trifluoromethyl- or 2-bromo-4-trifluoromethylphenyl group and the remaining general symbols are as defined above. / y A compound according to any one of claims 1 to 3, wherein R ⁴ is 2,6-dichloro-4-trifluoromethylchloro-4-trifluoromethoxyphenyl, and the remainder were as defined above. 1 to 6, in which or in the 2,6-general syntax (a) R ⁵ SO, 2 ' 9. A process -ziúcefrín formula I according to 1, characterized in that in the production of compounds wherein R ³⁸ is a radical R ⁵ SO or R ^S, R ³ is an unsubstituted not aminoskupi118, R ¹ is cyano or acetyl group, and the remaining general symbols are as defined above, a compound of formula II Cl, 14 _and C = NNHR ^θ / (II) in which R ⁸ is cyano or acetyl, R ⁴ is as defined in claim 1, reacted with a compound of formula R ² CH ₂ CN wherein R ² is defined as in Claim 1, or that the {54 (b) for the production zľúéenín, wherein R ² is a radical R ^S and R ³ is an amino group of formula -NR ^e R ⁷ wherein R ⁶ and R ⁷ are each hydrogen or straight or branched chain alkyl, alkenylalkyl or alkynylalkyl group as defined in claim 1 and the other substituents are as defined above, the corresponding compound of formula I, in which the place of R @ ² is H, with a compound of formula III R ³ - SCI (III) in which R ³ is defined as in Claim 1, 119 or that (c) ru, fluorine, for the manufacture zlúčenín-, wherein R ^X is Cl ² is a radical R _{^a, and} SO, SO ^p R R or ^S, R ³ is amino and the other substituents are as defined above a compound of formula IV c = c _x NC Y (IV) in which X and Y are both chlorine or fluorine, is reacted with a phenylhydrazine of formula V R 1 NHNH (V) wherein R ⁴ is as defined in claim 1, or an acid addition salt thereof, or that / p / uo'-h (d) (1) for the preparation of compounds wherein R ² represents a residue R 3 ^is S, R ^x is chloro, bromo, iodo or fluoro, cyano or nitro, R ³ is amino and the remaining radicals are as defined above, corresponding to the compound of formula I wherein thiocyanato is present at R ² , react with a compound of formula VI (VI) IS <··; ·. '· ·' ·. ·! .. Zr ·. ·. ΓΛ.ί ·.-Ϊ́ ': ¾¾ 120 R ^s - Mg - X ¹ in which R ^p is as defined in claim 1 and X ¹ represents a halogen atom or a compound of formula IX R ⁹ - CC - Liv where (IX) the group R ⁹ -CC ^- corresponds to the radical R ^s of the general formula I or that (d) (2) for the manufacture of compounds in which R ² represents the radical R ^s S except 1 -alkenyltioskupiny a 1-alkynylthio, and the other substituents are as defined above, the corresponding compound of formula I, in which the place of R @ ² is tiokyanatoskupina, is reacted with a base or a reducing agent in the presence of a reagent of the formula VII _{R | x = t} (VII) in which ^R * is as defined in Claim 1 for R ^p with the exception of 1-alkenyl and 1-Vej alkynyl group, and X ² represents a halogen atom or a base in the presence of a compound of formula VIIA F ₂ C = C (Z) (Z ·) (VIIA) 121 in which Z represents a fluorine, chlorine or bromine atom; Z * is as defined for Z or represents a trifluoromethyl group, or in that (d) (3) for the production -zlúčeníir, wherein R ^S is not 1-alkenylthio or 1-alkynylthio and the other substituents are as defined above, reductive alkylation a disulfide of formula VIII (VIII) wherein R ^x, R ³ and R ⁴ are as defined in Claim 1, with a reducing agent in the presence of a base and a halide of formula VII, wherein ^R, is as defined, or in that (e) for the production ffEuQegán- in wherein R ² is a radical R ^a SO or SO ₃ R ^a, and the other substituents are as defined above, oxidizing the sulfur atom of the corresponding compound of formula I, wherein R ² is a radical R ^{and an} s, or in that 122 (f) for the production ziúéenín, wherein R ¹ is F, Cl, Br, I, CN or coupling the corresponding compound of formula I, in which in place of the symbol ^Rx is amino and R ³ is H or an amino group, a diazotized amino group in place of the symbol ^Rx is a known process into a fluorine, chlorine, bromine or iodine atom or a cyano whether nitro, or for the production of compounds wherein R ³ is halogen, diazotising the corresponding compound of formula I, wherein R ³ is amino and the diazotized amino group R ³ is converted to a halogen atom in a known manner, or (g) to produce compounds wherein R ^x is a fluorine atom or a cyano group and R ³ is a hydrogen atom or an amino group, and the remaining general symbols have the meanings given above, the halide of the formula I in which m R ¹ represents a chlorine or bromine atom, reacted with an alkali metal fluoride or an alkali metal cyanide to convert a chlorine or bromine atom into a fluorine or cyano atom, or (h) for the production of Srtúčerrin in which R ^x represents a nitro group and R ² is a radical R ⁵ SO 2 or R ^a SO, and the other substituents are as defined above, the corresponding compound of formula I, in which the place of R @ ^x is unsubstituted amino, R ² is a radical R ^a SO, ^R SO or R 3 ^with S and R ³ represents a hydrogen atom or an amino group, reacted with an oxidizing agent to convert the unsubstituted amino group R ¹ into a nitro group, or 123 (i) for the preparation of compounds in which R ^{@ 1} is cyano, R ^{@ 3} is hydrogen or amino and the remaining radicals are as defined above, dehydrates the corresponding compound of formula I in which carbamoyl is present at R ^{@ 1} group or that f (j) for the preparation of compounds in which R ¹ is acetyl, R ³ is hydrogen or amino and the remaining general symbols are as defined above, corresponding to the nitrile of formula I in which R ¹ is cyano or the corresponding ester in which at a point of the symbol ^Rx is an alkoxycarbonyl group of formula CO ^ R, wherein R is straight or branched alkyl of 1 to 6 carbon atoms, or the corresponding carboxylic acid, in which the place of R @ ^x is a carboxy group, is reacted with. methyl lithium, or the corresponding nitrile of the formula I, wherein R ¹ is a cyano group, or ester thereof, in which the place of R @ ¹ are as defined above alkoxycarbonyl group of formula _CO2 R, is reacted with a Grignard reagent CH ₃ MgX ³ wherein X ³ is a halogen atom or that (k) an alcohol corresponding to formula I is oxidized in place of the symbol R to produce compounds in which R ¹ is an acetyl group and R ³ and all the rest of the symbols are as defined above. ^x is a hydroxyethyl group by oxidizing agent or (1) for the preparation of compounds wherein R ^x is a formyl group and R ³ and all the remaining general symbols are as defined above, corresponding to the nitrile of formula I wherein R ^x is cyano, reacted with a reducing agent followed by acid hydrolysis, or with Raney124 - in formic acid to convert the cyano group to the formyl group, or (m) converting a compound of formula I wherein -R ³ is an amino group of the formula -NR ^e R ⁷ and the remaining radicals as defined above into the corresponding methods by known methods a compound of formula (I) wherein R ³ is another amino group of formula -NR ⁶ R ⁷ , or is a compound of formula (I); (n) for the preparation of compounds of the formula I in which R ³ represents a straight or branched (C 2 -C 5) alkoxymethyleneamino group, optionally substituted on the methylene residue by a straight or branched (C 1 -C 4) alkyl group, and the remaining general symbols have the meaning given above , the corresponding compound of formula I wherein R ³ is an unsubstituted amino group is reacted with a trisalkoxyalkane, (I) or (o) for the preparation of compounds in which R ³ represents an -NHCH 2 R ¹⁶ radical, wherein R ¹⁶ represents a hydrogen atom or a straight or branched (C 1 -C 4) alkyl group and the remaining general symbols are as defined above, the corresponding compound of formula I wherein R ³ is a radical -N = C (oR ¹⁷⁾ R ^{1 s,} wherein R ¹⁷ is straight or branched alkyl of 1 to 4 carbon atoms and R @ ^xe is as defined above, is reacted with reducing agent, or in that (p) for preparing compounds wherein R ^ of ^x is formyl, acetyl, cyano or nitro, R ³ is F and the other substituents are as 125 as defined above, carries out the halogen exchange of the corresponding compound of formula I in which R ³ is chlorine or bromine, or (q) for the preparation of chlorides in which R ³ is hydrogen and the remaining general symbols have as defined above, the corresponding compound of formula I wherein R ³ is amino is reacted with a diazotizing agent in a solvent at a temperature ranging from room temperature to reflux to convert the amino group R ³ to hydrogen, or (r) for the preparation of z-Compounds in which R ¹ is cyano or nitro, R ² is Ŕ ⁵ SO _and , R * and R ⁷ are in each case a straight or branched alkyl, alkenylalkyl or alkynylalkyl group containing up to 5 atoms alkyl, wherein R ⁷ may also be H, and the other substituents are as defined above, the dpovedajúca compound of formula I, wherein R ³ is halogen, is reacted with the corresponding amine of the formula R ⁶ R ⁷ NH, or dimethylhydrazine when the two symbols R ⁶ and R ⁷ are methyl, and optionally the following the compound of formula I obtained is converted into another compound of formula I. for the manufacture of another compound of formula XXV as the intermediate of the uenoins of formula I according to claim 9 126 XXV R ² 'is defined as R ² in claim 1 or is a hydrogen atom, thiocyanato, formyl, cyano or carboxyl group, further chain or branched alkoxycarbonyl having 2 to 7 carbon atoms or ditioskupinu connecting two pyrazole rings, R ³ 'has the meaning as R ³ in claim 1 or represents a diphenoxycarbonylamino group; ,. R ¹ 'has the meaning as R ^x in claim 1 or is amino, 1-hydroxyethyl, carboxyl, carbamoyl or a straight or branched alkoxycarbonyl or alkoxycarbonylamino group containing from 2 to 7 carbon atoms and R ⁴ is as defined in claim 1, with the exception of compounds of formula I and formula XXV, wherein R ⁴ is 2,6-dichloro-4-trifluoromethylphenyl, R ² 'is cyano, R ^x ' is cyano and R ³ · represents amino, acetylamido, dichloroacetamido, tert-butylcarbonylamino, propionamido, pentanamido, bis (ethoxycarbonyl) amino, ethoxycarbonylamino, methylamino or ethylamino, or in which: R ³ '' represents a chlorine atom, R ³ 'represents an amino group, tert-butylcarbonylamino group, bis (ethoxycarbonyl) amino group 127 or ethoxycarbonylamino and the remaining general symbols are as defined above or in which R ¹ represents a bromine or iodine atom, an amino group or ethoxycarbonyl alkyl group, R ³ is amino, and · the other substituents are as defined above, or wherein R ¹ 'represents a fluorine atom, R ³ ' represents a hydrogen atom or an amino group, and the remaining general symbols are as defined above, or in which R ¹ 'is nitro, amino, tert-butoxycarbonylamino or ethoxycarbonyl, R ³ ' is hydrogen and the remaining general symbols are as defined above, or in which R ⁴ is 2,4,6-trichlorophenyl, 2-chloro-4-trifluoromethylphenyl or 2,6-dichloro-4-trifluoromethoxyphenyl,> ¹ ', R ³ ' is cyano, R ¹ 'is cyano and R ³ represents an amino group or in which R ⁴ is 2,6-dichloro-4-trifluoromethoxyphenyl, R ³ 'is cyano, R ^x ' is chlorine and R ³ 'is amino, or in which R ⁴ is 2,6-dichloro-4-trifluoromethylphenyl, R ³ 'is methanesulfonyl, R ^x * is carboxyl, carbamoyl or ethoxycarbonyl and R ³ ' is amino. 11. An insecticidal composition comprising, as active ingredient, a compound of the formula I as claimed in claim 1 in combination with one or more compatible diluents or carriers. 128 Use of the compounds of the formula I as claimed in claims 1 to 8 for controlling insects.